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1.
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
2.
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 , Imagem por Ressonância Magnética , Masculino , Meduloblastoma/radioterapia , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Espaço Subaracnóideo/diagnóstico por imagem , Resultado do Tratamento
3.
Int J Radiat Oncol Biol Phys ; 106(2): 255-260, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31654784

RESUMO

PURPOSE: Whole brain radiation therapy (WBRT) remains a commonly used cancer treatment, although controversy exists regarding the optimal dose/fractionation to optimize intracranial tumor control and minimize resultant cognitive deficits. METHODS AND MATERIALS: NCCTG N107C [Alliance]/CEC.3 randomized 194 patients with brain metastases to either stereotactic radiosurgery alone or WBRT after surgical resection. Among the 92 patients receiving WBRT, sites predetermined the dose/fractionation that would be used for all patients treated at that site (either 30 Gy in 10 fractions or 37.5 Gy in 15 fractions). Analyses were performed using Kaplan-Meier estimates, log rank tests, and Fisher's exact tests. RESULTS: Among 92 patients treated with surgical resection and adjuvant WBRT, 49 were treated with 30 Gy in 10 fractions (53%), and 43 were treated with 37.5 Gy in 15 fractions (47%). Baseline characteristics, including cognitive testing, were well balanced between groups with the exception of primary tumor type (lung cancer histology was more frequent with protracted WBRT: 72% vs 45%, P = .01), and 93% of patients completed the full course of WBRT. A more protracted WBRT dose regimen (37.5 Gy in 15 fractions) did not significantly affect time to cognitive failure (hazard ratio [HR], 0.9; 95% confidence interval [CI], 0.6-1.39; P = .66), surgical bed control (HR, 0.52 [95% CI, 0.22-1.25], P = .14), intracranial tumor control (HR, 0.56 [95% CI, 0.28-1.12], P = .09), or overall survival (HR, 0.72 [95% CI, 0.45-1.16], P = .18). Although there was no reported radionecrosis, there is a statistically significant increase in the risk of at least 1 grade ≥3 adverse event with 37.5 Gy in 15 fractions versus 30 Gy in 10 fractions (54% vs 31%, respectively, P = .03). CONCLUSIONS: This post hoc analysis does not demonstrate that protracted WBRT courses reduce the risk of cognitive deficit, improve tumor control in the hypoxic surgical cavity, or otherwise improve the therapeutic ratio. Adverse events were significantly higher with the lengthened course of WBRT. For patients with brain metastases where WBRT is recommended, shorter course hypofractionated regimens remain the current standard of care.


Assuntos
Neoplasias Encefálicas/radioterapia , Transtornos Cognitivos/prevenção & controle , Irradiação Craniana/normas , Melhoria de Qualidade , Radiocirurgia/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Intervalos de Confiança , Irradiação Craniana/efeitos adversos , Fracionamento da Dose de Radiação , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Radiocirurgia/efeitos adversos , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/normas
4.
Am J Clin Oncol ; 43(2): 128-132, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31764021

RESUMO

OBJECTIVE: Radiation therapy (RT) is the primary treatment of intracranial metastasis (ICM) from lung cancer (LC). Radiation necrosis (RN) has been reported post-RT with an incidence of 5% to 24%. We reviewed the spectrum of imaging changes in patients treated with RT for ICM from LC in an effort to identify potential risk factors for RN. METHODS: We reviewed 63 patients with LC and ICM who received RT (radiosurgery [stereotactic radiosurgery] with/without whole brain radiation therapy) at our institution between 2013 and 2018. Data evaluated included demographics, tumor type, ICM burden and location, chemotherapy, surgery, and RT details as well as treatment choices and outcomes. RESULTS: Of the 63 patients, clinical and radiographic criteria for RN were noted in 24 (38%) as early as 2 months and as late as 5 years posttreatment. Six patients required surgical resection due to refractory symptoms revealing pathology-proven RN and occasionally tumor. Patients were significantly more likely to develop RN if they had surgical resection of an ICM (45.8% vs. 20.5%, P=0.05). No differences were found in location, size, or genetic profile of lesions. In total, 80% of patients received treatment for symptoms and/or radiographic change. This was generally a combination of steroids, bevacizumab, laser interstitial thermal treatment, or surgical resection. Most patients required >1 treatment modality. CONCLUSIONS: This review of outcomes of RT for ICM in LC demonstrates a higher rate of RN than previously reported in the literature in those having had a surgical resection plus stereotactic radiosurgery. Our observation of RN as late as 5 years post-RT for ICM necessitates clinician awareness.


Assuntos
Neoplasias Encefálicas/radioterapia , Encéfalo/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma de Células Pequenas/radioterapia , Neoplasias Pulmonares/patologia , Lesões por Radiação/epidemiologia , Radiocirurgia/efeitos adversos , Adenocarcinoma/radioterapia , Adenocarcinoma/secundário , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/secundário , Carcinoma de Células Pequenas/secundário , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/secundário , Estudos de Coortes , Irradiação Craniana/efeitos adversos , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Necrose , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/etiologia , Lesões por Radiação/patologia , Estudos Retrospectivos , Fatores de Risco , Carga Tumoral
5.
In Vivo ; 34(1): 247-253, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31882485

RESUMO

BACKGROUND: We investigated acute adverse events in patients with brain metastases (BMs) of anaplastic lymphoma kinase-rearranged (ALKr) non-small cell lung cancer (NSCLC) treated with both cranial radiotherapy and tyrosine kinase inhibitors (TKIs) of ALK. PATIENTS AND METHODS: Acute AEs were retrospectively investigated in patients with BMs of ALKr-NSCLC who received both whole-brain radiotherapy (WBRT) and ALK-TKI. For comparison, they were also assessed in patients with epidermal growth factor receptor (EGFR)-mutated NSCLC and wild-type with neither ALK rearrangement nor EGFR mutation treated with WBRT. RESULTS: Two ALKr cases were consequently eligible. Grade 3 otitis media unexpectedly occurred in both cases, while there was one case out of 11 and one case out of 18 of grade 2 otitis media among the EGFR-mutated cases and wild-type cases (p=0.013), respectively. CONCLUSION: Concurrent treatment with WBRT and ALK-TKI may be associated with acute severe ear toxicity in patients with BMs of ALKr-NSCLC.


Assuntos
Adenocarcinoma de Pulmão/terapia , Quinase do Linfoma Anaplásico/antagonistas & inibidores , Quinase do Linfoma Anaplásico/genética , Neoplasias Encefálicas/terapia , Quimiorradioterapia/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Rearranjo Gênico , Radiodermatite/etiologia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Antineoplásicos/efeitos adversos , Biomarcadores Tumorais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Irradiação Craniana/efeitos adversos , Crizotinibe/efeitos adversos , Receptores ErbB/genética , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Estudos Retrospectivos
6.
BMC Neurol ; 19(1): 232, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31578138

RESUMO

BACKGROUND: Radiation therapy can cause cerebral arteriopahty, resulting in ischemic stroke. We document late-delayed cerebral arteriopathy by high-resolution magnetic resonance imaging (HR-MRI) in a middle aged man who had cranial irradiation 19 years earlier. CASE PRESENTATION: A 45-year-old man was diagnosed with frontal lobe glioma 19 years ago and was treated with radiation after surgical resection. He was admitted to our hospital with an acute cerebral infarction in November 8, 2017. Traditional MRI examination and HR-MRI (sagittal, reconstruction of coronal and axial) were performed at admission. He was treated with prednisone (30 mg/day) and clinical symptoms disappeared after 3 months by telephone follow-up. Our patient complained of dizziness and blurred vision and traditional MRI examination indicated acute ischemic stroke in temporal lobe and occipital lobe and microbleeds. In order to define the exact mechanism of stroke, blood tests, auto-immune screening and thrombophilia were performed and results were normal. Electrocardiography and echocardiography were negative and cardiogenic cerebral embolism was excluded. In cerebrospinal fluid (CSF) examination, level of albumin and IgG were elevated. HR-MRI showed vessel wall thickening in T1-weighted imaging, narrow lumen in proton density imaging and vessel wall concentric enhancement in contrast-enhanced T1- weighted imaging. Combined with radiotherapy history, the patient was diagnosed with radioactive vasculitis. CONCLUSION: Radiation-induced cerebrovascular damages could be a lasting progress, which we cannot ignore. HR-MRI can provide sensitive and accurate diagnostic assessment of radiation-induced arteritis and may be a useful tool for the screening of causes of cryptogenic stroke.


Assuntos
Irradiação Craniana/efeitos adversos , Lesões por Radiação/diagnóstico por imagem , Vasculite do Sistema Nervoso Central/diagnóstico por imagem , Vasculite do Sistema Nervoso Central/etiologia , Neoplasias Encefálicas/radioterapia , Glioma/radioterapia , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia
7.
Dokl Biol Sci ; 487(1): 95-97, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31571073

RESUMO

The visually driven instrumental conditioning of a single monkey (Macaca mulatta) was conducted after single-dose cranial irradiation with high-energy protons. The monkey executed saccades toward the visual stimuli and then responded by manually pressing right or left lever for stimuli in right or left half-field, respectively. The percentage of correct responses with dominant right hand exceeded the percentage of such responses with left hand and temporarily decreased two months after irradiation. A month later, the percentage of correct right-hand responses returned to the level before irradiation. No significant dynamic was found for changes in percentage of correct left-hand responses. The proton irradiation effect on right-hand responses suggests possible short-term disturbances in the eye-hand coordination for right handedness while the visual perception remains unaffected.


Assuntos
Irradiação Craniana/efeitos adversos , Prótons/efeitos adversos , Desempenho Psicomotor , Animais , Condicionamento Operante , Radiação Cósmica/efeitos adversos , Lateralidade Funcional , Macaca mulatta , Masculino
8.
Crit Rev Oncol Hematol ; 143: 95-101, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31563079

RESUMO

Extensive disease Small cell lung cancer (ED-SCLC) represents a very aggressive malignancy in which brain metastases (BM) are quite common. Clinical trials on prophylactic cranial irradiation (PCI) have showed a clear decrease in the risk of developing BM but conflicting results concerning a possible survival advantage. A landmark European Organisation for Research and Treatment of Cancer (EORTC) prospective trial, as well as multitude of retrospective series confirm survival benefit after PCI. Recently, a Japan Clinical Oncology Group (JCOG) study did not find such survival benefit, provided that non-irradiated patients are closely followed by MRI. Henceforth, the role of PCI in this population has been questioned, on the ground of the possible absence of survival benefit, leading to a gradual shift in oncology practice. We performed a review of the literature on the subject of PCI in ED-SCLC patients. We conclude that PCI could still play a crucial role in these patients, considering not only a possible survival benefit, but also alternative endpoints, such as improved local control, delay in the onset of symptomatic BM and lower toxicity of a prophylactic- rather than an eventual active-intent treatment. Individualized attitude should be discussed with patients, while addressing all arguments in favour and against PCI.


Assuntos
Neoplasias Encefálicas/prevenção & controle , Neoplasias Encefálicas/radioterapia , Irradiação Craniana/métodos , Neoplasias Pulmonares/radioterapia , Carcinoma de Pequenas Células do Pulmão/radioterapia , Neoplasias Encefálicas/secundário , Irradiação Craniana/efeitos adversos , Humanos , Neoplasias Pulmonares/patologia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/patologia
9.
Pediatr Blood Cancer ; 66(12): e27983, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31502379

RESUMO

BACKGROUND: Germ cell tumors (GCT) arising from non-midline structures (basal ganglia, thalamus, and posterior fossa) are rare. Although patients with midline (pineal and suprasellar) germinoma have excellent survival with chemotherapy and whole ventricular irradiation (WVI), germinoma in non-midline locations have traditionally been treated with craniospinal irradiation (CSI) or whole brain irradiation (WBI) to achieve similar outcomes. However, CSI and WBI are associated with significant long-term neuropsychological sequelae. METHODS: We describe the clinical and neuropsychological outcomes of patients with non-midline germinoma treated at the Children's Hospital Los Angeles between 1990 and 2015. RESULTS: Nine patients had basal ganglia/thalamic germinoma and one patient had a cerebellar primary. Eight patients received chemotherapy followed by reduced dose/volume irradiation, whereas two patients received chemotherapy alone as upfront therapy. One patient in the chemotherapy alone group relapsed after 4.3 years and was salvaged with CSI plus boost. The overall survival for the entire cohort was 100% at a median follow-up of 8.5 years. Neuropsychological data were available for six patients at a median of five months (baseline) and 4.2 years (follow-up) post-diagnosis. At four-year follow-up, data available revealed intact overall cognitive ability, verbal memory, and executive functioning, but persistent deficits in fine motor function. Comparison of baseline to follow-up suggests a downward trend in working memory, planning/problem-solving, verbal memory, and visuospatial integration. CONCLUSION: Chemotherapy followed by reduced dose/volume of irradiation is an effective strategy resulting in long-term survival in patients with non-midline germinoma. Neuropsychological data suggest relatively minimal morbidity over time.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Sistema Nervoso Central/terapia , Quimiorradioterapia/efeitos adversos , Irradiação Craniana/efeitos adversos , Germinoma/terapia , Doenças do Sistema Nervoso/patologia , Adolescente , Adulto , Neoplasias do Sistema Nervoso Central/patologia , Criança , Pré-Escolar , Feminino , Seguimentos , Germinoma/patologia , Humanos , Masculino , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/psicologia , Testes Neuropsicológicos , Prognóstico , Dosagem Radioterapêutica , Estudos Retrospectivos , Adulto Jovem
10.
Psychooncology ; 28(11): 2166-2173, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31418491

RESUMO

OBJECTIVE: Although brain radiation therapy (RT) impacts cognitive function, little is known about the subset of survivors with minimal cognitive deficits. This study compares the characteristics of patients receiving brain irradiation as part of cancer treatment with minimal cognitive deficits to those with poorer cognitive functioning. METHODS: Adults at least 6 months postbrain RT (N = 198) completed cognitive measures of attention, memory, and executive functions. Cognitive functioning was categorized into better- and poorer-performing groups, with better-performing survivors scoring no worse than 1.5 standard deviations below the published normative mean on all cognitive measures. Logistic regression was used to identify variables associated with better-performing group membership. RESULTS: Approximately 25% of the sample met the criteria for the better-performing group. In unadjusted analyses, RT type (whole brain irradiation and partial brain irradiation), sedating medications, and fatigue were independently associated with cognition. Sociodemographic and other clinical characteristics were not significant. In adjusted analyses, only fatigue remained significantly associated with group membership (OR = 1.05, 95% CI = 1.01-1.09, P = .009). CONCLUSIONS: There is a subgroup of survivors with minimal long-term cognitive deficits despite undergoing a full course of brain RT as part of cancer treatment. Lower fatigue had the strongest association with better cognitive performance. Interventions targeting cancer-related fatigue may help buffer the neurotoxic effects of brain RT.


Assuntos
Sobreviventes de Câncer/psicologia , Transtornos Cognitivos/psicologia , Disfunção Cognitiva/etiologia , Irradiação Craniana/efeitos adversos , Neoplasias/radioterapia , Adulto , Encéfalo/fisiopatologia , Cognição/efeitos da radiação , Transtornos Cognitivos/etiologia , Disfunção Cognitiva/psicologia , Fadiga/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/psicologia , Dosagem Radioterapêutica
11.
Radiat Oncol ; 14(1): 152, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31455428

RESUMO

AIM: To quantify the prevalence of brain metastases involving the hypothalamic-pituitary (HT-P) area. INTRODUCTION: Cognitive impairment and fatigue are common side effects of whole brain irradiation (WBI) comprising the quality of life (QoL) for survivors. While the former is related to radiation-induced hippocampal injury, the latter could be secondary to hormonal disbalance as a consequence of radiation of the HT-P area. Thus, sparing both regions from higher irradiation doses could reduce these sequelae. METHODS: T1 contrast medium enhanced magnetic resonance imaging (MRI) scans of 865 patients with brain metastases (4,280 metastases) were reviewed. HT-P area was individually contoured with a margin of 5 mm in order to evaluate the prevalence of brain metastases in this region. RESULTS: Involvement of the hypothalamic region was found in 26 patients (involvement rate of 3% for patients and 1% for metastases), involvement of the pituitary gland in 9 patients (1% for patients and < 1% for metastases). Binary logistical regression analysis revealed the presence of > 10 brain metastases as the only factor associated with hypothalamic involvement while no distinct factor was associated with an involvement of the pituitary gland. CONCLUSION: The low prevalence of metastases within the HT-P area in patients with brain metastases calls for further studies examining whether sparing of this region might improve patients QoL.


Assuntos
Neoplasias Encefálicas/radioterapia , Irradiação Craniana/efeitos adversos , Hipocampo/patologia , Neoplasias/radioterapia , Neoplasias Hipofisárias/epidemiologia , Lesões por Radiação/etiologia , Planejamento da Radioterapia Assistida por Computador/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/secundário , Sobreviventes de Câncer/estatística & dados numéricos , Feminino , Alemanha/epidemiologia , Hipocampo/efeitos da radiação , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Tratamentos com Preservação do Órgão , Órgãos em Risco/efeitos da radiação , Neoplasias Hipofisárias/secundário , Prevalência , Prognóstico , Qualidade de Vida , Lesões por Radiação/patologia , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Taxa de Sobrevida
12.
Pediatr Blood Cancer ; 66(11): e27947, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31418996

RESUMO

BACKGROUND: Survivors of childhood brain tumors are prone to sleep and neurocognitive problems. Effective interventions to improve neurocognitive functioning are largely lacking. In general, sleep problems are negatively related to neurocognitive functioning, but this relationship is unclear in survivors of childhood brain tumors. Therefore, the occurrence of sleep problems, potential risk factors, and the relation between sleep and executive functioning were evaluated. PROCEDURE: Baseline data of a randomized controlled trial on the effectiveness of neurofeedback were used. Childhood brain tumor survivors 8-18 years of age with parent-reported neurocognitive complaints ≥2 years after treatment were eligible. Parents completed the Sleep Disturbance Scale for Children. Executive functioning was assessed by parents and teachers (Behavior Rating Inventory of Executive Functioning). Multiple linear regression analyses were used to examine sociodemographic and medical characteristics and emotional difficulties and hyperactivity/inattention (Strength and Difficulties Questionnaire) as potential risk factors for sleep problems, and to assess the association between sleep and executive functioning. RESULTS: Forty-eight percent of survivors (n = 82, 7.0 ± 3.6 years post diagnosis, age 13.8 ± 3.2 years) had sleep problems and scored significantly worse than the norm on the subscales Initiating and Maintaining Sleep, Excessive Somnolence, and the total scale (effect sizes 0.58-0.92). Emotional problems and/or hyperactivity/inattention were independent potential risk factors. Sleep problems were associated with worse parent-reported executive functioning. CONCLUSIONS: Sleep problems occur among half of childhood brain tumor survivors with neurocognitive problems, and are associated with worse executive functioning. Future studies should focus on the development of sleep interventions for this population, to improve sleep as well as executive functioning.


Assuntos
Dano Encefálico Crônico/etiologia , Neoplasias Encefálicas/psicologia , Sobreviventes de Câncer/psicologia , Transtornos do Comportamento Infantil/etiologia , Transtornos Cognitivos/etiologia , Transtornos do Sono-Vigília/etiologia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Dano Encefálico Crônico/psicologia , Neoplasias Encefálicas/terapia , Criança , Transtornos do Comportamento Infantil/epidemiologia , Transtornos do Comportamento Infantil/psicologia , Transtornos Cognitivos/epidemiologia , Irradiação Craniana/efeitos adversos , Craniotomia/efeitos adversos , Emoções , Função Executiva , Humanos , Testes Neuropsicológicos , Prevalência , Psicologia , Índice de Gravidade de Doença , Transtornos do Sono-Vigília/epidemiologia
13.
Int J Radiat Oncol Biol Phys ; 105(4): 773-783, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31408667

RESUMO

PURPOSE: We used quantitative magnetic resonance imaging to prospectively analyze the association between microstructural damage to memory-associated structures within the medial temporal lobe and longitudinal memory performance after brain radiation therapy (RT). METHODS AND MATERIALS: Patients with a primary brain tumor receiving fractionated brain RT were enrolled on a prospective trial (n = 27). Patients underwent high-resolution volumetric brain magnetic resonance imaging, diffusion-weighted imaging, and neurocognitive testing before and 3, 6, and 12 months post-RT. Medial temporal lobe regions (hippocampus; entorhinal, parahippocampal, and temporal pole white matter [WM]) were autosegmented, quantifying volume and diffusion biomarkers of WM integrity (mean diffusivity [MD]; fractional anisotropy [FA]). Reliable change indices measured changes in verbal (Hopkins Verbal Learning Test-Revised) and visuospatial (Brief Visuospatial Memory Test-Revised [BVMT-R]) memory. Linear mixed-effects models assessed longitudinal associations between imaging parameters and memory. RESULTS: Visuospatial memory significantly declined at 6 months post-RT (mean reliable change indices, -1.3; P = .012). Concurrent chemotherapy and seizures trended toward a significant association with greater decline in visuospatial memory (P = .053 and P = .054, respectively). Higher mean dose to the left temporal pole WM was significantly associated with decreased FA (r = -0.667; P = .002). Over all time points, smaller right hippocampal volume (P = .021), lower right entorhinal FA (P = .023), greater right entorhinal MD (P = .047), and greater temporal pole MD (BVMT-R total recall, P = .003; BVMT-R delayed recall, P = .042) were associated with worse visuospatial memory. The interaction between right entorhinal MD (BVMT-R total recall, P = .021; BVMT-R delayed recall, P = .004) and temporal pole FA (BVMT-R delayed recall, P = .024) significantly predicted visuospatial memory performance. CONCLUSIONS: Brain tumor patients exhibited visuospatial memory decline post-RT. Microstructural damage to critical memory regions, including the hippocampus and medial temporal lobe WM, were associated with post-RT memory decline. The integrity of medial temporal lobe structures is critical to memory performance post-RT, representing possible avoidance targets for memory preservation.


Assuntos
Neoplasias Encefálicas/radioterapia , Irradiação Craniana/efeitos adversos , Transtornos da Memória/etiologia , Memória/efeitos da radiação , Lesões por Radiação/complicações , Lobo Temporal/efeitos da radiação , Adulto , Idoso , Agnosia/diagnóstico , Agnosia/etiologia , Anisotropia , Antineoplásicos/efeitos adversos , Neoplasias Encefálicas/tratamento farmacológico , Irradiação Craniana/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Fracionamento da Dose de Radiação , Córtex Entorrinal/diagnóstico por imagem , Córtex Entorrinal/efeitos da radiação , Feminino , Neuroimagem Funcional , Hipocampo/diagnóstico por imagem , Hipocampo/efeitos da radiação , Humanos , Masculino , Transtornos da Memória/diagnóstico , Rememoração Mental/efeitos dos fármacos , Rememoração Mental/efeitos da radiação , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estudos Prospectivos , Convulsões/complicações , Substância Branca/diagnóstico por imagem , Substância Branca/efeitos da radiação , Adulto Jovem
14.
J Clin Neurosci ; 68: 39-44, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31399318

RESUMO

The standard medical care of glioblastoma (GBM) patients with good performance status is based on focal brain radiotherapy (40-60 Gy) with concurrent temozolomide (TMZ) followed by adjuvant TMZ. Newly diagnosed multifocal and/or multicentric GBM (M/M GBM) cases are usually treated with TMZ alone: whole brain chemoradiotherapy (CRT) is avoided for safety reasons. To our knowledge, no study has investigated the safety and efficacy of whole-brain radiotherapy (WBRT) with concurrent TMZ in M/M GBM patients. This retrospective study sought to assess the role of WBRT associated with concurrent TMZ followed by TMZ alone in this population. Eleven patients with pathologically proven M/M GBM (≥3 lobes) were treated with WBRT between April 2009 and September 2017. The median age was 50 years [34-74]. The median dose of radiotherapy was 45 Gy at 1.8 Gy per fraction over 37 days [29-41], with concurrent daily TMZ at the dose of 75 mg/m2. This treatment was followed by adjuvant monthly TMZ (150 mg/m2-D1-D5). All pathology slides and radiology images were reviewed. The median overall and progression-free survival times for all patients were 10 months [4-25] and 5 months [3-21], respectively. There was no grade 3-4 toxicity due to radiotherapy. One patient stopped the TMZ during the radiochemotherapy period and 9 patients received adjuvant TMZ with a median number of 5 cycles [2-8]. Our study supports the safety and the efficacy of WBRT with TMZ in newly diagnosed M/M GBM. Larger prospective studies are needed to support our results.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Neoplasias Encefálicas/terapia , Quimiorradioterapia/métodos , Irradiação Craniana/métodos , Glioblastoma/terapia , Temozolomida/administração & dosagem , Adulto , Idoso , Antineoplásicos Alquilantes/efeitos adversos , Neoplasias Encefálicas/patologia , Quimiorradioterapia/efeitos adversos , Irradiação Craniana/efeitos adversos , Feminino , Glioblastoma/mortalidade , Glioblastoma/patologia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Temozolomida/efeitos adversos
15.
Anticancer Res ; 39(8): 4273-4277, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366517

RESUMO

BACKGROUND/AIM: For treatment of brain metastases, a patient's survival prognosis should be considered. Existing survival scores appear complex and require complete tumor staging. For many patients, a faster and simpler tool would be helpful. PATIENTS AND METHODS: This retrospective study investigated the prognostic value of the number of pre-treatment symptoms plus eight other factors on survival of patients irradiated for brain metastases. Other factors included whole-brain radiotherapy (WBRT) regimen, age, gender, performance score, primary tumor type, number of brain metastases, extracranial metastases, and interval between cancer diagnosis and WBRT. RESULTS: The number of symptoms (p=0.002) and all other factors were significantly associated with survival on univariate analyses. On multivariate analysis, all factors but the number of symptoms (p=0.47) and primary tumor type (p=0.48) were significant. CONCLUSION: Since the number of symptoms was not an independent predictor of survival, it cannot replace existing scoring tools and may only serve for orientation.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias/radioterapia , Prognóstico , Idoso , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/secundário , Irradiação Craniana/efeitos adversos , Feminino , Humanos , Avaliação de Estado de Karnofsky , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias/classificação , Neoplasias/patologia
16.
J Neurooncol ; 144(2): 351-358, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31302830

RESUMO

INTRODUCTION: This study evaluated an association between whole brain volume loss and neurocognitive decline following prophylactic cranial irradiation (PCI) for limited-stage small-cell lung cancer (SCLC). METHODS: This was a secondary analysis of a prospective clinical trial that accrued patients at a single institution from 2013 to 2016. Patients with limited-stage SCLC treated with standard chemo-radiation received PCI 25 Gy/10 fractions, with mean hippocampal dose limited to < 8 Gy. Whole brain volumes were measured using MR imaging obtained before and at 6, 12, 18, and 24 months after PCI. Verbal memory was measured by the Hopkins Verbal Learning Test-Revised (HVLT-R) before and at 6 and 12 months after PCI. Univariate and multivariate linear regression evaluated associations between changes in whole brain volume and verbal memory. RESULTS: Twenty-two patients enrolled. The median whole brain volume before PCI was 1301 mL. Subsequent reduction in whole brain volume was greatest at 18 months after PCI (median change - 23 mL, range - 142 to 20, p = 0.03). At 6 months after PCI, reduction in volume was independently associated with decline in verbal memory, measured by two components of the HVLT-R (Delayed Recall: 0.06/mL volume change, p = 0.046; Percent Retained: 0.66/mL volume change, p = 0.030), when controlling for education and global cognitive function at baseline. CONCLUSION: This is the first study to correlate reduction in whole brain volume and decline in neurocognitive function following whole brain radiation therapy (WBRT). This suggests that loss of brain volume after WBRT may be clinically significant and subsequently impact cognition and quality of life.


Assuntos
Neoplasias Encefálicas/patologia , Transtornos Cognitivos/patologia , Irradiação Craniana/efeitos adversos , Hipocampo , Tratamentos com Preservação do Órgão/efeitos adversos , Lesões por Radiação/patologia , Carcinoma de Pequenas Células do Pulmão/radioterapia , Adulto , Idoso , Neoplasias Encefálicas/etiologia , Transtornos Cognitivos/etiologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Masculino , Rememoração Mental , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Lesões por Radiação/etiologia , Carcinoma de Pequenas Células do Pulmão/patologia , Carga Tumoral
18.
Cancer Radiother ; 23(5): 370-377, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31331843

RESUMO

PUPOSE: Medulloblastoma is the most common primary malignant central nervous system tumor in childhood, accounting for 16-25% of cases (1). New treatment approaches have led to improved survival rates; however toxicities are still a major concern. PATIENTS AND METHODS: Participants were selected from the records of patients who were treated with craniospinal irradiation for medulloblastoma. Between January 2008 and December 2012, 62 patients were diagnosed with medulloblastoma at the national institute of oncology Rabat, 27 patients were still alive at the time of the study, of which n=16 patients were included in the study. The mean age of patients at the time of the study was 9.6 years. All children were treated with radiation therapy and chemotherapy, according to standard protocols. Median follow-up between treatment and evaluation was 4 years. All the children were assessed with the Wechsler Intelligence Scale for Children - fourth Edition (WISC-IV) three to five years after completion of radiotherapy. The test was administered by two well-trained psychologists in a distraction-free environment. The scoring was then reviewed by a psychologist from Brooklyn College. RESULTS: The mean standard score Full-Scale Intelligence Quotient (FSIQ) (M=63, SD=12.6) was found to be in the extremely low range and in the 1st percentile rank (PR), compared to the general population. All the measured primary index scales were below typical performance: verbal comprehension (M=67.7, SD=13.1), perceptual reasoning (M=63.5, SD=13.8) and processing speed (M=62.7, SD=15.5) were all found to be in the extremely low range, while xorking memory (M=75.5, SD=10.8) was found to be in the borderline range compared to the general population. To identify factors influencing the results, we performed both univariate and multivariate analyses. Age at the time of radiotherapy, initial clinical stage, total cranial radiotherapy dose, socioeconomic status, and the time of evaluation were identified as significantly impacting cognitive scores in the univariate analysis. In the multivariate analysis, only age at the time of radiotherapy and initial clinical stage remained factors significantly impacting cognitive outcomes with P=0.001 and P<0.001 respectively. CONCLUSION: Our study is evidence that tremendous efforts are still to be made in low-income countries to correctly measure neurocognitive dysfunction in medulloblastoma survivors and to prepare those patients to a typical life after the completion of treatment.


Assuntos
Neoplasias Cerebelares/radioterapia , Irradiação Craniana/efeitos adversos , Meduloblastoma/radioterapia , Transtornos Neurocognitivos/etiologia , Fatores Etários , Antineoplásicos/uso terapêutico , Neoplasias Cerebelares/tratamento farmacológico , Criança , Pré-Escolar , Terapia Combinada , Seguimentos , Substância Cinzenta/lesões , Substância Cinzenta/patologia , Hipocampo/lesões , Hipocampo/patologia , Humanos , Meduloblastoma/tratamento farmacológico , Transtornos da Memória/etiologia , Transtornos da Memória/patologia , Transtornos Neurocognitivos/patologia , Tamanho do Órgão , Modelos de Riscos Proporcionais , Escalas de Wechsler , Substância Branca/lesões , Substância Branca/patologia
19.
Cancer Radiother ; 23(5): 432-438, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31331844

RESUMO

Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (3 to 5% of all non-small cell lung cancers) carries a particularly high risk of central nervous system dissemination (60% to 90%). As the use of ALK inhibitors improves treatment outcomes over chemotherapy, the determent of central nervous system metastases has become an increasingly relevant therapeutic dilemma considering young age and possible extended overall survival. The goal of brain metastases management is to optimize both overall survival and quality of life, with the high priority of neurocognitive function preservation. Unfortunately in the first year on crizotinib, the pioneering ALK inhibitors, approximately one third of these patients fail in the central nervous system, which is explained by an inadequate central nervous system drug penetration through the blood-brain barrier. Central nervous system-directed radiotherapy represents the most important strategy to control intracranial disease burden and extend the survival benefit with crizotinib. The role of whole brain irradiation in the treatment of brain metastases diminishes, as this technique is associated with the risk of neurocognitive decline. Stereotactic radiotherapy represents an alternative technique that delivers ablative doses of ionizing radiation to the limited volume of oligometastatic brain disease, offering sparing of the adjacent brain parenchyma and reduced neurotoxicity. The next generation ALK inhibitors were designed to cross the blood-brain barrier more efficiently than crizotinib and achieve higher concentration in the cerebrospinal fluid, offering prominent ability to control central nervous system spread. In the phase III ALEX trial the intracranial control was significantly better with alectinib as compared to crizotinib and it translated into survival benefit. Other next generation ALK inhibitors (i.e. ceritinib, brigatinib, lorlatinib) also demonstrated promising activity in the central nervous system.


Assuntos
Quinase do Linfoma Anaplásico/antagonistas & inibidores , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares , Neoplasias Meníngeas/secundário , Proteínas de Neoplasias/antagonistas & inibidores , Quinase do Linfoma Anaplásico/análise , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/enzimologia , Neoplasias Encefálicas/radioterapia , Carbazóis/farmacocinética , Carbazóis/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Cisplatino/administração & dosagem , Ensaios Clínicos como Assunto , Terapia Combinada , Irradiação Craniana/efeitos adversos , Irradiação Craniana/métodos , Crizotinibe/farmacocinética , Crizotinibe/uso terapêutico , Gerenciamento Clínico , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Meníngeas/enzimologia , Neoplasias Meníngeas/radioterapia , Camundongos , Terapia de Alvo Molecular , Proteínas de Neoplasias/análise , Transtornos Neurocognitivos/etiologia , Transtornos Neurocognitivos/prevenção & controle , Estudos Observacionais como Assunto , Proteínas de Fusão Oncogênica/análise , Proteínas de Fusão Oncogênica/antagonistas & inibidores , Pemetrexede/administração & dosagem , Piperidinas/farmacocinética , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/farmacocinética , Inibidores de Proteínas Quinases/uso terapêutico , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos
20.
Int J Radiat Oncol Biol Phys ; 105(4): 765-772, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31351194

RESUMO

PURPOSE: Dry eye is not typically considered a toxicity of whole brain radiation therapy (WBRT). We analyzed dry eye syndrome as part of a prospective study of patient-reported outcomes after WBRT. METHODS AND MATERIALS: Patients receiving WBRT to 25 to 40 Gy were enrolled on a study with dry mouth as the primary endpoint and dry eye syndrome as a secondary endpoint. Patients received 3-dimensional WBRT using opposed lateral fields. Per standard practice, lacrimal glands were not prospectively delineated. Patients completed the Subjective Evaluation of Symptom of Dryness (SESoD, scored 0-4, with higher scores representing worse dry eye symptoms) at baseline, immediately after WBRT (EndRT), and at 1 month (1M), 3 months, and 6 months. Patients with baseline SESoD ≥3 (moderate dry eye) were excluded. The endpoints analyzed were ≥1-point and ≥2-point increase in SESoD score at 1M. Lacrimal glands were retrospectively delineated with fused magnetic resonance imaging scans. RESULTS: One hundred patients were enrolled, 70 were eligible for analysis, and 54 were evaluable at 1M. Median bilateral lacrimal V20Gy was 79%. At 1M, 17 patients (32%) had a ≥1-point increase in SESoD score, and 13 (24%) a ≥2-point increase. Lacrimal doses appeared to be associated with an increase in SESoD score of both ≥1 point (V10Gy: P = .042, odds ratio [OR] 1.09/%; V20Gy: P = .071, OR 1.03/%) and ≥2 points (V10Gy: P = .038, OR 1.15/%; V20Gy: P = .063, OR 1.04/%). The proportion with increase in dry eye symptoms at 1M for lacrimal V20Gy ≥79% versus <79% was 46% versus 15%, respectively, for ≥1 point SESoD increase (P = .02) and 36% versus 12%, respectively, for ≥2 point SESoD increase (P = .056). CONCLUSIONS: Dry eye appears to be a relatively common, dose/volume-dependent acute toxicity of WBRT. Minimization of lacrimal gland dose may reduce this toxicity, and patients should be counseled regarding the existence of this potential side effect and treatments for dry eye.


Assuntos
Neoplasias Encefálicas/radioterapia , Irradiação Craniana/efeitos adversos , Síndromes do Olho Seco/etiologia , Aparelho Lacrimal/efeitos da radiação , Medidas de Resultados Relatados pelo Paciente , Adulto , Idoso , Idoso de 80 Anos ou mais , Irradiação Craniana/métodos , Síndromes do Olho Seco/prevenção & controle , Feminino , Humanos , Aparelho Lacrimal/diagnóstico por imagem , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Dosagem Radioterapêutica , Xerostomia/etiologia , Adulto Jovem
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