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1.
N Engl J Med ; 389(2): 118-126, 2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37437144

RESUMO

BACKGROUND: Craniopharyngiomas, primary brain tumors of the pituitary-hypothalamic axis, can cause clinically significant sequelae. Treatment with the use of surgery, radiation, or both is often associated with substantial morbidity related to vision loss, neuroendocrine dysfunction, and memory loss. Genotyping has shown that more than 90% of papillary craniopharyngiomas carry BRAF V600E mutations, but data are lacking with regard to the safety and efficacy of BRAF-MEK inhibition in patients with papillary craniopharyngiomas who have not undergone previous radiation therapy. METHODS: Eligible patients who had papillary craniopharyngiomas that tested positive for BRAF mutations, had not undergone radiation therapy previously, and had measurable disease received the BRAF-MEK inhibitor combination vemurafenib-cobimetinib in 28-day cycles. The primary end point of this single-group, phase 2 study was objective response at 4 months as determined with the use of centrally determined volumetric data. RESULTS: Of the 16 patients in the study, 15 (94%; 95% confidence interval [CI], 70 to 100) had a durable objective partial response or better to therapy. The median reduction in the volume of the tumor was 91% (range, 68 to 99). The median follow-up was 22 months (95% CI, 19 to 30) and the median number of treatment cycles was 8. Progression-free survival was 87% (95% CI, 57 to 98) at 12 months and 58% (95% CI, 10 to 89) at 24 months. Three patients had disease progression during follow-up after therapy had been discontinued; none have died. The sole patient who did not have a response stopped treatment after 8 days owing to toxic effects. Grade 3 adverse events that were at least possibly related to treatment occurred in 12 patients, including rash in 6 patients. In 2 patients, grade 4 adverse events (hyperglycemia in 1 patient and increased creatine kinase levels in 1 patient) were reported; 3 patients discontinued treatment owing to adverse events. CONCLUSIONS: In this small, single-group study involving patients with papillary craniopharyngiomas, 15 of 16 patients had a partial response or better to the BRAF-MEK inhibitor combination vemurafenib-cobimetinib. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT03224767.).


Assuntos
Antineoplásicos , Craniofaringioma , Neoplasias Hipofisárias , Humanos , Craniofaringioma/tratamento farmacológico , Craniofaringioma/genética , Progressão da Doença , Quinases de Proteína Quinase Ativadas por Mitógeno/antagonistas & inibidores , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/genética , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genética , Vemurafenib/efeitos adversos , Vemurafenib/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Indução de Remissão
2.
Blood ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38776489

RESUMO

Delays and risks associated with neurosurgical biopsies preclude timely diagnosis and treatment of central nervous system (CNS) lymphoma and other CNS neoplasms. We prospectively integrated targeted rapid genotyping of cerebrospinal fluid (CSF) into the evaluation of 70 patients with CNS lesions of unknown etiology. Participants underwent genotyping of CSF-derived DNA using a qPCR-based approach for parallel detection of single-nucleotide variants in the MYD88, TERT promoter, IDH1, IDH2, BRAF and H3F3A genes within 80 minutes of sample acquisition. Canonical mutations were detected in 42% of patients with neoplasms, including cases of primary and secondary CNS lymphoma, glioblastoma, IDH-mutant brainstem glioma and H3K27M-mutant diffuse midline glioma. Genotyping results eliminated the need for surgical biopsies in 7/33 (21.2%) cases of newly diagnosed neoplasms, resulting in significantly accelerated initiation of disease-directed treatment (median 3 vs 12 days; p = 0.027). This assay was then implemented in a Clinical Laboratory Improvement Amendments (CLIA) environment, with 2-day median turnaround for diagnosis of central nervous system lymphoma from 66 patients across 4 clinical sites. Our study prospectively demonstrates that targeted rapid CSF genotyping influences oncologic management for suspected CNS tumors.

3.
Blood ; 138(5): 382-386, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-33735913

RESUMO

Diagnosing primary central nervous system lymphoma (PCNSL) frequently requires neurosurgical biopsy due to nonspecific radiologic features and the low yield of cerebrospinal fluid (CSF) studies. We characterized the clinical evaluation of suspected PCNSL (N = 1007 patients) and designed a rapid multiplexed genotyping assay for MYD88, TERT promoter, IDH1/2, H3F3A, and BRAF mutations to facilitate the diagnosis of PCNSL from CSF and detect other neoplasms in the differential diagnosis. Among 159 patients with confirmed PCNSL, the median time to secure a diagnosis of PCNSL was 10 days, with a range of 0 to 617 days. Permanent histopathology confirmed PCNSL in 142 of 152 biopsies (93.4%), whereas CSF analyses were diagnostic in only 15/113 samplings (13.3%). Among 86 archived clinical specimens, our targeted genotyping assay accurately detected hematologic malignancies with 57.6% sensitivity and 100% specificity (95% confidence interval [CI]: 44.1% to 70.4% and 87.2% to 100%, respectively). MYD88 and TERT promoter mutations were prospectively identified in DNA extracts of CSF obtained from patients with PCNSL and glioblastoma, respectively, within 80 minutes. Across 132 specimens, hallmark mutations indicating the presence of malignancy were detected with 65.8% sensitivity and 100% specificity (95% CI: 56.2%-74.5% and 83.9%-100%, respectively). This targeted genotyping approach offers a rapid, scalable adjunct to reduce diagnostic and treatment delays in PCNSL.


Assuntos
Neoplasias do Sistema Nervoso Central , Técnicas de Genotipagem , Linfoma não Hodgkin , Mutação , Proteínas de Neoplasias , Reação em Cadeia da Polimerase em Tempo Real , Adulto , Neoplasias do Sistema Nervoso Central/líquido cefalorraquidiano , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/genética , Feminino , Humanos , Linfoma não Hodgkin/líquido cefalorraquidiano , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/genética , Proteínas de Neoplasias/líquido cefalorraquidiano , Proteínas de Neoplasias/genética
4.
Neurosurg Focus ; 55(5): E12, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37913538

RESUMO

OBJECTIVE: Racial and socioeconomic disparities in neuro-oncological care for patients with brain tumors remain underexplored. This study aimed to analyze county-level disparities in glioblastoma (GBM) care in the United States, focusing on access to surgery and the use of adjuvant temozolomide chemotherapy and radiation therapy. METHODS: Using repeated cross-sectional data from the Surveillance, Epidemiology, and End Results 17 database; the Area Health Resources File; and the American Community Survey, from 2010 to 2019, the authors performed multivariate regression analyses to understand the associations between county-level racial and socioeconomic characteristics, as well as the rates of surgery performed, delays in surgery, and use of adjuvant chemotherapy and radiation therapy for newly diagnosed GBM. RESULTS: In total, 29,609 GBM patients from 602 different US counties over a decade were included in this study. Counties with lower rates of surgery for GBM were associated with a higher percentage of Black residents (coefficient [CE] -0.001, 95% CI -0.002 to 0; p < 0.05) and being located in the Midwest (CE -0.132, 95% CI -0.195 to -0.069; p < 0.001) or West (CE -0.127, 95% CI -0.189 to -0.065; p < 0.001) relative to the Northeast. Counties with delayed surgical treatment were more likely to lack neurosurgeons (adjusted OR [aOR] 2.52, 95% CI 1.77-3.60; p < 0.001), have a higher percentage of Black residents (aOR 1.011, 95% CI 1.00-1.02; p < 0.05), and be located in the Midwest (aOR 3.042, 95% CI 1.12-8.24; p < 0.05) or West (aOR 3.175, 95% CI 1.12-8.97 p < 0.05). Counties with high rates of adjuvant radiation therapy were less likely to have higher percentages of Black residents (aOR 0.987, 95% CI 0.980-0.995; p < 0.01) and uninsured individuals (aOR 0.962, 95% CI 0.937-0.987; p < 0.01). CONCLUSIONS: Counties without neurosurgeons and those with a higher percentage of Black patients have delays in surgical care and demonstrate lower overall rates of surgery and adjuvant therapy for GBM. This study underscores the need for targeted interventions and policies that address structural barriers in healthcare access, improve equitable distribution of the neurosurgery workforce, and ensure timely and comprehensive GBM care to all populations.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Estados Unidos/epidemiologia , Glioblastoma/epidemiologia , Glioblastoma/cirurgia , Estudos Transversais , Fatores Socioeconômicos , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/cirurgia , Recursos em Saúde
5.
Proc Natl Acad Sci U S A ; 115(36): E8388-E8394, 2018 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-30082399

RESUMO

Aggressive neurosurgical resection to achieve sustained local control is essential for prolonging survival in patients with lower-grade glioma. However, progression in many of these patients is characterized by local regrowth. Most lower-grade gliomas harbor isocitrate dehydrogenase 1 (IDH1) or IDH2 mutations, which sensitize to metabolism-altering agents. To improve local control of IDH mutant gliomas while avoiding systemic toxicity associated with metabolic therapies, we developed a precision intraoperative treatment that couples a rapid multiplexed genotyping tool with a sustained release microparticle (MP) drug delivery system containing an IDH-directed nicotinamide phosphoribosyltransferase (NAMPT) inhibitor (GMX-1778). We validated our genetic diagnostic tool on clinically annotated tumor specimens. GMX-1778 MPs showed mutant IDH genotype-specific toxicity in vitro and in vivo, inducing regression of orthotopic IDH mutant glioma murine models. Our strategy enables immediate intraoperative genotyping and local application of a genotype-specific treatment in surgical scenarios where local tumor control is paramount and systemic toxicity is therapeutically limiting.


Assuntos
Neoplasias Encefálicas , Cianetos/farmacologia , Genótipo , Glioma , Guanidinas/farmacologia , Isocitrato Desidrogenase/genética , Terapia de Alvo Molecular/métodos , Mutação , Proteínas de Neoplasias/genética , Animais , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/enzimologia , Neoplasias Encefálicas/genética , Sistemas de Liberação de Medicamentos/métodos , Feminino , Glioma/tratamento farmacológico , Glioma/enzimologia , Glioma/genética , Humanos , Masculino , Camundongos , Camundongos SCID , Ensaios Antitumorais Modelo de Xenoenxerto
6.
JAMA ; 325(10): 942-951, 2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33687463

RESUMO

Importance: Cervical spondylotic myelopathy is the most common cause of spinal cord dysfunction worldwide. It remains unknown whether a ventral or dorsal surgical approach provides the best results. Objective: To determine whether a ventral surgical approach compared with a dorsal surgical approach for treatment of cervical spondylotic myelopathy improves patient-reported physical functioning at 1 year. Design, Setting, and Participants: Randomized clinical trial of patients aged 45 to 80 years with multilevel cervical spondylotic myelopathy enrolled at 15 large North American hospitals from April 1, 2014, to March 30, 2018; final follow-up was April 15, 2020. Interventions: Patients were randomized to undergo ventral surgery (n = 63) or dorsal surgery (n = 100). Ventral surgery involved anterior cervical disk removal and instrumented fusion. Dorsal surgery involved laminectomy with instrumented fusion or open-door laminoplasty. Type of dorsal surgery (fusion or laminoplasty) was at surgeon's discretion. Main Outcomes and Measures: The primary outcome was 1-year change in the Short Form 36 physical component summary (SF-36 PCS) score (range, 0 [worst] to 100 [best]; minimum clinically important difference = 5). Secondary outcomes included 1-year change in modified Japanese Orthopaedic Association scale score, complications, work status, sagittal vertical axis, health resource utilization, and 1- and 2-year changes in the Neck Disability Index and the EuroQol 5 Dimensions score. Results: Among 163 patients who were randomized (mean age, 62 years; 80 [49%] women), 155 (95%) completed the trial at 1 year (80% at 2 years). All patients had surgery, but 5 patients did not receive their allocated surgery (ventral: n = 1; dorsal: n = 4). One-year SF-36 PCS mean improvement was not significantly different between ventral surgery (5.9 points) and dorsal surgery (6.2 points) (estimated mean difference, 0.3; 95% CI, -2.6 to 3.1; P = .86). Of 7 prespecified secondary outcomes, 6 showed no significant difference. Rates of complications in the ventral and dorsal surgery groups, respectively, were 48% vs 24% (difference, 24%; 95% CI, 8.7%-38.5%; P = .002) and included dysphagia (41% vs 0%), new neurological deficit (2% vs 9%), reoperations (6% vs 4%), and readmissions within 30 days (0% vs 7%). Conclusions and Relevance: Among patients with cervical spondylotic myelopathy undergoing cervical spinal surgery, a ventral surgical approach did not significantly improve patient-reported physical functioning at 1 year compared with outcomes after a dorsal surgical approach. Trial Registration: ClinicalTrials.gov Identifier: NCT02076113.


Assuntos
Vértebras Cervicais/cirurgia , Laminectomia/métodos , Medidas de Resultados Relatados pelo Paciente , Doenças da Medula Espinal/cirurgia , Fusão Vertebral/métodos , Espondilose/cirurgia , Idoso , Idoso de 80 Anos ou mais , Vértebras Cervicais/diagnóstico por imagem , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Radiografia , Medula Espinal/diagnóstico por imagem , Resultado do Tratamento
7.
N Engl J Med ; 374(15): 1424-34, 2016 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-27074067

RESUMO

BACKGROUND: The comparative effectiveness of performing instrumented (rigid pedicle screws affixed to titanium alloy rods) lumbar spinal fusion in addition to decompressive laminectomy in patients with symptomatic lumbar grade I degenerative spondylolisthesis with spinal stenosis is unknown. METHODS: In this randomized, controlled trial, we assigned patients, 50 to 80 years of age, who had stable degenerative spondylolisthesis (degree of spondylolisthesis, 3 to 14 mm) and symptomatic lumbar spinal stenosis to undergo either decompressive laminectomy alone (decompression-alone group) or laminectomy with posterolateral instrumented fusion (fusion group). The primary outcome measure was the change in the physical-component summary score of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36; range, 0 to 100, with higher scores indicating better quality of life) 2 years after surgery. The secondary outcome measure was the score on the Oswestry Disability Index (range, 0 to 100, with higher scores indicating more disability related to back pain). Patients were followed for 4 years. RESULTS: A total of 66 patients (mean age, 67 years; 80% women) underwent randomization. The rate of follow-up was 89% at 1 year, 86% at 2 years, and 68% at 4 years. The fusion group had a greater increase in SF-36 physical-component summary scores at 2 years after surgery than did the decompression-alone group (15.2 vs. 9.5, for a difference of 5.7; 95% confidence interval, 0.1 to 11.3; P=0.046). The increases in the SF-36 physical-component summary scores in the fusion group remained greater than those in the decompression-alone group at 3 years and at 4 years (P=0.02 for both years). With respect to reductions in disability related to back pain, the changes in the Oswestry Disability Index scores at 2 years after surgery did not differ significantly between the study groups (-17.9 in the decompression-alone group and -26.3 in the fusion group, P=0.06). More blood loss and longer hospital stays occurred in the fusion group than in the decompression-alone group (P<0.001 for both comparisons). The cumulative rate of reoperation was 14% in the fusion group and 34% in the decompression-alone group (P=0.05). CONCLUSIONS: Among patients with degenerative grade I spondylolisthesis, the addition of lumbar spinal fusion to laminectomy was associated with slightly greater but clinically meaningful improvement in overall physical health-related quality of life than laminectomy alone. (Funded by the Jean and David Wallace Foundation and others; SLIP ClinicalTrials.gov number, NCT00109213.).


Assuntos
Laminectomia , Vértebras Lombares/cirurgia , Fusão Vertebral , Estenose Espinal/cirurgia , Espondilolistese/cirurgia , Idoso , Idoso de 80 Anos ou mais , Descompressão Cirúrgica , Avaliação da Deficiência , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Reoperação/estatística & dados numéricos , Estenose Espinal/complicações , Espondilolistese/complicações , Resultado do Tratamento
8.
Acta Neuropathol ; 136(5): 779-792, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30123936

RESUMO

Progressive meningiomas that have failed surgery and radiation have a poor prognosis and no standard therapy. While meningiomas are more common in females overall, progressive meningiomas are enriched in males. We performed a comprehensive molecular characterization of 169 meningiomas from 53 patients with progressive/high-grade tumors, including matched primary and recurrent samples. Exome sequencing in an initial cohort (n = 24) detected frequent alterations in genes residing on the X chromosome, with somatic intragenic deletions of the dystrophin-encoding and muscular dystrophy-associated DMD gene as the most common alteration (n = 5, 20.8%), along with alterations of other known X-linked cancer-related genes KDM6A (n =2, 8.3%), DDX3X, RBM10 and STAG2 (n = 1, 4.1% each). DMD inactivation (by genomic deletion or loss of protein expression) was ultimately detected in 17/53 progressive meningioma patients (32%). Importantly, patients with tumors harboring DMD inactivation had a shorter overall survival (OS) than their wild-type counterparts [5.1 years (95% CI 1.3-9.0) vs. median not reached (95% CI 2.9-not reached, p = 0.006)]. Given the known poor prognostic association of TERT alterations in these tumors, we also assessed for these events, and found seven patients with TERT promoter mutations and three with TERT rearrangements in this cohort (n = 10, 18.8%), including a recurrent novel RETREG1-TERT rearrangement that was present in two patients. In a multivariate model, DMD inactivation (p = 0.033, HR = 2.6, 95% CI 1.0-6.6) and TERT alterations (p = 0.005, HR = 3.8, 95% CI 1.5-9.9) were mutually independent in predicting unfavorable outcomes. Thus, DMD alterations identify a subset of progressive/high-grade meningiomas with worse outcomes.


Assuntos
Distrofina/genética , Deleção de Genes , Neoplasias Meníngeas/genética , Meningioma/genética , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral/patologia , Linhagem Celular Tumoral/ultraestrutura , Estudos de Coortes , Progressão da Doença , Distrofina/metabolismo , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/patologia , Meningioma/diagnóstico por imagem , Meningioma/patologia , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex , RNA Mensageiro/metabolismo , Cromatina Sexual/genética , Telomerase/genética , Telomerase/metabolismo , Sequenciamento do Exoma
9.
Lancet Oncol ; 18(8): 1049-1060, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28687377

RESUMO

BACKGROUND: Whole brain radiotherapy (WBRT) is the standard of care to improve intracranial control following resection of brain metastasis. However, stereotactic radiosurgery (SRS) to the surgical cavity is widely used in an attempt to reduce cognitive toxicity, despite the absence of high-level comparative data substantiating efficacy in the postoperative setting. We aimed to establish the effect of SRS on survival and cognitive outcomes compared with WBRT in patients with resected brain metastasis. METHODS: In this randomised, controlled, phase 3 trial, adult patients (aged 18 years or older) from 48 institutions in the USA and Canada with one resected brain metastasis and a resection cavity less than 5·0 cm in maximal extent were randomly assigned (1:1) to either postoperative SRS (12-20 Gy single fraction with dose determined by surgical cavity volume) or WBRT (30 Gy in ten daily fractions or 37·5 Gy in 15 daily fractions of 2·5 Gy; fractionation schedule predetermined for all patients at treating centre). We randomised patients using a dynamic allocation strategy with stratification factors of age, duration of extracranial disease control, number of brain metastases, histology, maximal resection cavity diameter, and treatment centre. Patients and investigators were not masked to treatment allocation. The co-primary endpoints were cognitive-deterioration-free survival and overall survival, and analyses were done by intention to treat. We report the final analysis. This trial is registered with ClinicalTrials.gov, number NCT01372774. FINDINGS: Between Nov 10, 2011, and Nov 16, 2015, 194 patients were enrolled and randomly assigned to SRS (98 patients) or WBRT (96 patients). Median follow-up was 11·1 months (IQR 5·1-18·0). Cognitive-deterioration-free survival was longer in patients assigned to SRS (median 3·7 months [95% CI 3·45-5·06], 93 events) than in patients assigned to WBRT (median 3·0 months [2·86-3·25], 93 events; hazard ratio [HR] 0·47 [95% CI 0·35-0·63]; p<0·0001), and cognitive deterioration at 6 months was less frequent in patients who received SRS than those who received WBRT (28 [52%] of 54 evaluable patients assigned to SRS vs 41 [85%] of 48 evaluable patients assigned to WBRT; difference -33·6% [95% CI -45·3 to -21·8], p<0·00031). Median overall survival was 12·2 months (95% CI 9·7-16·0, 69 deaths) for SRS and 11·6 months (9·9-18·0, 67 deaths) for WBRT (HR 1·07 [95% CI 0·76-1·50]; p=0·70). The most common grade 3 or 4 adverse events reported with a relative frequency greater than 4% were hearing impairment (three [3%] of 93 patients in the SRS group vs eight [9%] of 92 patients in the WBRT group) and cognitive disturbance (three [3%] vs five [5%]). There were no treatment-related deaths. INTERPRETATION: Decline in cognitive function was more frequent with WBRT than with SRS and there was no difference in overall survival between the treatment groups. After resection of a brain metastasis, SRS radiosurgery should be considered one of the standards of care as a less toxic alternative to WBRT for this patient population. FUNDING: National Cancer Institute.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Transtornos Cognitivos/etiologia , Recidiva Local de Neoplasia/diagnóstico por imagem , Radiocirurgia , Atividades Cotidianas , Adolescente , Adulto , Neoplasias Encefálicas/secundário , Progressão da Doença , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Feminino , Seguimentos , Humanos , Análise de Intenção de Tratamento , Imageamento por Ressonância Magnética , Masculino , Metastasectomia , Pessoa de Meia-Idade , Qualidade de Vida , Radiocirurgia/efeitos adversos , Radioterapia Adjuvante , Taxa de Sobrevida , Adulto Jovem
10.
Acta Neurochir (Wien) ; 159(4): 733-738, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28188418

RESUMO

BACKGROUND: Evidence of a high interobserver variability of the subjective House-Brackmann facial nerve grading system (HBGS) would justify cost- and time-consuming technological enhancements of objective classifications for facial nerve paresis. METHOD: A total of 112 patients were recruited for a randomized multi-center trial to investigate the efficacy of prophylactic nimodipine treatment in vestibular schwannoma (VS) surgery. For the present investigation both treatment groups were pooled for the assessment of facial nerve function preoperatively, in the early postoperative course and 1 year after the surgery. Facial nerve function was documented photographically at rest and in motion and classified according to the HBGS by three independent observers (neurosurgeon, neurologist, ENT) and by the investigator of each center. RESULTS: Interobserver variability was considerably different with respect to the three time points depending upon the severity of facial nerve paresis. Preoperative facial nerve function was normal or only mildly impaired (HB grade I or II) and was assessed consistently in 97%. Facial nerve function deteriorated during the early postoperative course and was subsequently documented without dissent in only 36%, with one grade difference in 45%, two grade difference in 17% and three grade difference in 2%. One year after surgery, facial nerve function predominantly improved resulting in a consistent assessment in 66%. Differing ratings were observed in 34% with one grade deviation in 88% and of two grades in 12%. Patients with differing ratings of two or more grades exhibited considerably worse facial nerve function (p < 0.001). CONCLUSIONS: The HBGS produced comparable results between different observers in patients with normal or only mildly impaired facial nerve function. Interobserver variability increased depending on the severity of facial nerve paresis. The results suggest that the HBGS does not promote uniformity of reporting and comparison of outcomes in patients with moderate or severe facial nerve paresis.


Assuntos
Ensaios Clínicos como Assunto/normas , Nervo Facial/patologia , Paralisia Facial/patologia , Exame Neurológico/normas , Complicações Pós-Operatórias/patologia , Adulto , Idoso , Nervo Facial/fisiopatologia , Paralisia Facial/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuroma Acústico/cirurgia , Variações Dependentes do Observador , Complicações Pós-Operatórias/etiologia , Índice de Gravidade de Doença , Adulto Jovem
11.
Ann Surg ; 264(1): 81-6, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26501698

RESUMO

OBJECTIVE: To determine whether patients who learned the views of an expert surgeons' panel's assessment of equipoise between 2 alternative operative treatments had increased likelihood of consenting to randomization. BACKGROUND: Difficulty obtaining patient consent to randomization is an important barrier to conducting surgical randomized clinical trials, the gold standard for generating clinical evidence. METHODS: Observational study of the rate of patient acceptance of randomization within a 5-center randomized clinical trial comparing lumbar spinal decompression versus lumbar spinal decompression plus instrumented fusion for patients with symptomatic grade I degenerative lumbar spondylolisthesis with spinal stenosis. Eligible patients were enrolled in the trial and then asked to accept randomization. A panel of 10 expert spine surgeons was formed to review clinical information and images for individual patients to provide an assessment of suitability for randomization. The expert panel vote was disclosed to the patient by the patient's surgeon before the patient decided whether to accept randomization or not. RESULTS: Randomization acceptance among eligible patients without expert panel review was 40% (19/48) compared with 81% (47/58) among patients undergoing expert panel review (P < 0.001). Among expert-reviewed patients, randomization acceptance was 95% when all experts or all except 1 voted for randomization, 75% when 2 experts voted against randomization, and 20% with 3 or 4 votes against (P < 0.001 for trend). CONCLUSIONS: Patients provided with an expert panel's assessment of their own suitability for randomization were twice as likely to agree to randomization compared with patients receiving only their own surgeon's recommendation.


Assuntos
Laminectomia/métodos , Vértebras Lombares , Estenose Espinal/cirurgia , Espondilolistese/cirurgia , Idoso , Idoso de 80 Anos ou mais , Descompressão Cirúrgica/métodos , Feminino , Seguimentos , Humanos , Laminectomia/instrumentação , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Estenose Espinal/diagnóstico por imagem , Espondilolistese/diagnóstico por imagem , Resultado do Tratamento , Estados Unidos
12.
Neurosurg Focus ; 41(6): E2, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27903124

RESUMO

Craniopharyngiomas are rare intracranial neoplasms that pose clinical challenges due to their location adjacent to vital structures. The authors have previously shown high mutation rates of BRAF V600E in papillary craniopharyngioma and of CTNNB1 in adamantinomatous craniopharyngioma. These activating driver mutations are potential therapeutic targets, and the authors have recently reported a significant response to BRAF/MEK inhibition in a patient with multiply recurrent PCP. As these targetable mutations warrant prospective research, the authors will be conducting a national National Cancer Institute-sponsored multicenter clinical trial to investigate BRAF/MEK inhibition in the treatment of craniopharyngioma. In this new era of genomic discovery, the treatment paradigm of craniopharyngioma is likely to change.


Assuntos
Craniofaringioma/diagnóstico por imagem , Craniofaringioma/terapia , Gerenciamento Clínico , Marcação de Genes/tendências , Genômica/tendências , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/terapia , Biomarcadores Tumorais/genética , Ensaios Clínicos como Assunto/métodos , Craniofaringioma/genética , Humanos , Mutação/genética , Neoplasias Hipofisárias/genética , beta Catenina/genética
14.
JAMA ; 316(4): 401-409, 2016 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-27458945

RESUMO

IMPORTANCE: Whole brain radiotherapy (WBRT) significantly improves tumor control in the brain after stereotactic radiosurgery (SRS), yet because of its association with cognitive decline, its role in the treatment of patients with brain metastases remains controversial. OBJECTIVE: To determine whether there is less cognitive deterioration at 3 months after SRS alone vs SRS plus WBRT. DESIGN, SETTING, AND PARTICIPANTS: At 34 institutions in North America, patients with 1 to 3 brain metastases were randomized to receive SRS or SRS plus WBRT between February 2002 and December 2013. INTERVENTIONS: The WBRT dose schedule was 30 Gy in 12 fractions; the SRS dose was 18 to 22 Gy in the SRS plus WBRT group and 20 to 24 Gy for SRS alone. MAIN OUTCOMES AND MEASURES: The primary end point was cognitive deterioration (decline >1 SD from baseline on at least 1 cognitive test at 3 months) in participants who completed the baseline and 3-month assessments. Secondary end points included time to intracranial failure, quality of life, functional independence, long-term cognitive status, and overall survival. RESULTS: There were 213 randomized participants (SRS alone, n = 111; SRS plus WBRT, n = 102) with a mean age of 60.6 years (SD, 10.5 years); 103 (48%) were women. There was less cognitive deterioration at 3 months after SRS alone (40/63 patients [63.5%]) than when combined with WBRT (44/48 patients [91.7%]; difference, -28.2%; 90% CI, -41.9% to -14.4%; P < .001). Quality of life was higher at 3 months with SRS alone, including overall quality of life (mean change from baseline, -0.1 vs -12.0 points; mean difference, 11.9; 95% CI, 4.8-19.0 points; P = .001). Time to intracranial failure was significantly shorter for SRS alone compared with SRS plus WBRT (hazard ratio, 3.6; 95% CI, 2.2-5.9; P < .001). There was no significant difference in functional independence at 3 months between the treatment groups (mean change from baseline, -1.5 points for SRS alone vs -4.2 points for SRS plus WBRT; mean difference, 2.7 points; 95% CI, -2.0 to 7.4 points; P = .26). Median overall survival was 10.4 months for SRS alone and 7.4 months for SRS plus WBRT (hazard ratio, 1.02; 95% CI, 0.75-1.38; P = .92). For long-term survivors, the incidence of cognitive deterioration was less after SRS alone at 3 months (5/11 [45.5%] vs 16/17 [94.1%]; difference, -48.7%; 95% CI, -87.6% to -9.7%; P = .007) and at 12 months (6/10 [60%] vs 17/18 [94.4%]; difference, -34.4%; 95% CI, -74.4% to 5.5%; P = .04). CONCLUSIONS AND RELEVANCE: Among patients with 1 to 3 brain metastases, the use of SRS alone, compared with SRS combined with WBRT, resulted in less cognitive deterioration at 3 months. In the absence of a difference in overall survival, these findings suggest that for patients with 1 to 3 brain metastases amenable to radiosurgery, SRS alone may be a preferred strategy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00377156.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Transtornos Cognitivos/etiologia , Cognição/efeitos da radiação , Irradiação Craniana , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Terapia Combinada/métodos , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Radiocirurgia , Análise de Sobrevida , Sobreviventes , Fatores de Tempo
19.
J Neurooncol ; 119(3): 593-600, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25081975

RESUMO

The Biennial Satellite Tumor Symposium is the flagship meeting of the AANS/CNS Section on Tumors. The year 2013 marked the 10th Tumor Section Biennial Satellite Tumor Symposium, a significant milestone warranting retrospection on the origin and development of the Satellite Tumor Symposium. This article provides a brief history of the Section on Tumors Biennial Satellite Tumor Symposium, including insights into the structure and evolution of the meeting, and recognizes some of the members of the AANS/CNS Section on Tumors who have contributed to Satellite meetings over the years.


Assuntos
Congressos como Assunto , Neoplasias , Neurocirurgia , Sociedades Médicas , Congressos como Assunto/história , História do Século XX , História do Século XXI , Humanos , Oncologia/história , Neurocirurgia/história , Sociedades Médicas/história , Estados Unidos
20.
J Neurooncol ; 119(3): 583-91, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24893731

RESUMO

A major goal of the Section on Tumors of the American Association of Neurological Surgery (AANS) and Congress of Neurological Surgeons (CNS) since it was founded in 1984 has been to foster both education and research in the field of brain tumor treatment and development. In support of this goal, the Section sponsors a number of awards, named lectures, and fellowships at the annual meetings of the AANS and CNS. In this article, we describe the awards given by the AANS/CNS Section on Tumors since its foundation, the recipients of the awards, and their philanthropic donors. The subsequent history of awardees and their work is briefly examined. Specifically for the Preuss and Mahaley Awards, this article also examines the rates of publication among the award-winning abstracts and achievement of grant funding by awardees.


Assuntos
Distinções e Prêmios , Bolsas de Estudo , Neoplasias , Neurocirurgia , Sociedades Médicas , Humanos , Internato e Residência , Neoplasias/terapia , Estados Unidos
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