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1.
Cancer ; 125(3): 424-433, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30359477

RESUMO

BACKGROUND: Repurposed memantine, mefloquine, and metformin have putative anticancer activity. The objective of this phase 1 study was to determine the maximum tolerated doses (MTDs) of combinations of these agents with temozolomide (TMZ). METHODS: Adults with newly diagnosed glioblastoma who completed chemoradiation were eligible. The patients were assigned to receive doublet, triplet, or quadruplet therapy with TMZ combined with mefloquine, memantine, and/or metformin. Dose-limiting toxicities (DLTs) were determined, using a 3 + 3 study design. RESULTS: Of 85 enrolled patients, 4 did not complete cycle 1 (the DLT observation period) for nontoxicity reasons, and 81 were evaluable for DLT. The MTDs for doublet therapy were memantine 20 mg twice daily, mefloquine 250 mg 3 times weekly, and metformin 850 mg twice daily. For triplet therapy, the MTDs were memantine 10 mg twice daily, mefloquine 250 mg 3 times weekly, and metformin 850 mg twice daily. For quadruplet therapy, the MTDs were memantine 10 mg twice daily, mefloquine 250 mg 3 times weekly, and metformin 500 mg twice daily. DLTs included dizziness (memantine) and gastrointestinal effects (metformin). Lymphopenia was the most common adverse event (66%). From study entry, the median survival was 21 months, and the 2-year survival rate was 43%. CONCLUSIONS: Memantine, mefloquine, and metformin can be combined safely with TMZ in patients with newly diagnosed glioblastoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas , Glioblastoma , Mefloquina/administração & dosagem , Memantina/administração & dosagem , Metformina/administração & dosagem , Temozolomida/administração & dosagem , Adulto , Idoso , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Quimioterapia Adjuvante , Ensaios Clínicos Fase II como Assunto/métodos , Feminino , Glioblastoma/diagnóstico , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Glioblastoma/radioterapia , Humanos , Masculino , Dose Máxima Tolerável , Mefloquina/efeitos adversos , Memantina/efeitos adversos , Metformina/efeitos adversos , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Radioterapia Adjuvante , Projetos de Pesquisa , Temozolomida/efeitos adversos , Resultado do Tratamento , Adulto Jovem
2.
J Neurooncol ; 128(1): 75-84, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26900076

RESUMO

Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiologic entity. Its management and outcome in the oncology population is limited because it is still difficult to identify despite an increasingly recognized occurrence. This is the largest retrospective study of PRES in cancer patients reported from a single institution. We explore the clinical manifestations and radiologic features to comprehensively assess PRES in order to prevent permanent neurologic deficits and mortality. We retrospectively identified 69 patients with cancer who developed PRES at MDACC between 01/2006 to 06/2012. Clinical and radiographic data were abstracted from their records and reviewed for our analysis. Mean age at PRES onset was 52 ± 17.8 years. Fifty-two (75 %; p < 0.001) patients were women. Most common diagnoses were leukemia (30 %) and lymphoma (12 %). Forty-eight (70 %) patients were treated with chemotherapy, 21 (30 %) bone marrow transplant and 14 (20 %) tacrolimus. Most common clinical presentation was seizures (67 %). PRES was associated with hypertension in 62 (90 %) patients. On brain MRI, 33 (44 %) patients had some evidence of hemorrhage, 22 (73 %) of these were thrombocytopenic. Thirty-five (51 %) patients fully recovered and 19 (28 %) had permanent neurological deficits. Morbidity and mortality were associated with continuation with offending agent, thrombocytopenia, variations in mean arterial pressure ≥20 mmHg, electrographic seizures at onset, atypical MRI pattern and delay in diagnostic imaging (7.4 ± 4.8 days vs. 1.9 ± 1.8 days; p = 0.031) as half of them did not receive a prompt intervention. Special attention should be given to patients who present with high-risk factors in order to prevent development of PRES or decrease patient morbidity and mortality. Management of PRES should be guided by the radiographic findings. Overall, early recognition, discontinuation of the offending agents, correction of thrombocytopenia and blood pressure control are still the main strategies to manage PRES.


Assuntos
Neoplasias/complicações , Síndrome da Leucoencefalopatia Posterior/complicações , Adulto , Idoso , Antineoplásicos/uso terapêutico , Antineoplásicos/toxicidade , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias/diagnóstico por imagem , Neoplasias/fisiopatologia , Neoplasias/terapia , Síndrome da Leucoencefalopatia Posterior/diagnóstico por imagem , Síndrome da Leucoencefalopatia Posterior/fisiopatologia , Síndrome da Leucoencefalopatia Posterior/terapia , Estudos Retrospectivos , Fatores de Risco , Convulsões/complicações , Convulsões/diagnóstico por imagem , Convulsões/fisiopatologia , Convulsões/terapia
3.
J Neurooncol ; 129(3): 487-494, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27406589

RESUMO

Antiangiogenic therapy can rapidly reduce vascular permeability and cerebral edema but high doses of bevacizumab may induce selective pressure to promote resistance. This trial evaluated the efficacy of low dose bevacizumab in combination with lomustine (CCNU) compared to standard dose bevacizumab in patients with recurrent glioblastoma. Patients (N = 71) with recurrent glioblastoma who previously received radiation and temozolomide were randomly assigned 1:1 to receive bevacizumab monotherapy (10 mg/kg) or low dose bevacizumab (5 mg/kg) in combination with lomustine (90 mg/m(2)). The primary end point was progression-free survival (PFS) based on a blinded, independent radiographic assessment of post-contrast T1-weighted and non-contrast T2/FLAIR weighted magnetic resonance imaging (MRI) using RANO criteria. For 69 evaluable patients, median PFS was not significantly longer in the low dose bevacizumab + lomustine arm (4.34 months, CI 2.96-8.34) compared to the bevacizumab alone arm (4.11 months, CI 2.69-5.55, p = 0.19). In patients with first recurrence, there was a trend towards longer median PFS time in the low dose bevacizumab + lomustine arm (4.96 months, CI 4.17-13.44) compared to the bevacizumab alone arm (3.22 months CI 2.5-6.01, p = 0.08). The combination of low dose bevacizumab plus lomustine was not superior to standard dose bevacizumab in patients with recurrent glioblastoma. Although the study was not designed to exclusively evaluate patients at first recurrence, a strong trend towards improved PFS was seen in that subgroup for the combination of low dose bevacizumab plus lomustine. Further studies are needed to better identify such subgroups that may most benefit from the combination treatment.


Assuntos
Antineoplásicos/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Lomustina/uso terapêutico , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Relação Dose-Resposta a Droga , Feminino , Glioblastoma/mortalidade , Humanos , Avaliação de Estado de Karnofsky , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
4.
Curr Oncol Rep ; 16(5): 383, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24595679

RESUMO

Posterior reversible encephalopathy syndrome is a well-recognized entity associated with a variety of benign and malignant conditions. This syndrome typically manifests itself with headache, visual loss, and seizures. Radiographic abnormalities consist of white matter edema involving the posterior parietal and occipital lobes, manifested as increased T2 and fluid-attenuated inversion recovery signal intensity on magnetic resonance imaging. In the last decade, there has been a reported increase in the incidence of posterior reversible encephalopathy syndrome in cancer patients. The diagnosis can be challenging in this patient population. Early recognition and initiation of appropriate therapy with removal of the causative agent is essential in order to prevent permanent neurologic sequelae.


Assuntos
Neoplasias/complicações , Síndrome da Leucoencefalopatia Posterior , Edema Encefálico/diagnóstico , Edema Encefálico/etiologia , Humanos , Hipertensão Maligna/complicações , Neuroimagem/métodos , Síndrome da Leucoencefalopatia Posterior/diagnóstico , Síndrome da Leucoencefalopatia Posterior/etiologia , Síndrome da Leucoencefalopatia Posterior/terapia
5.
Neurooncol Pract ; 11(4): 475-483, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39006516

RESUMO

Background: We observed rapid tumor progression following COVID-19 infection among patients with glioblastoma and sought to systematically characterize their disease course in a retrospective case-control study. Methods: Using an institutional database, we retrospectively identified a series of COVID-19-positive glioblastoma cases and matched them by age and sex 1:2 to glioblastoma controls who had a negative COVID-19 test during their disease course. Demographic and clinical data were analyzed. Hyperprogression was defined using modified response evaluation criteria in solid tumors criteria. Time to progression and overall survival were estimated using the Kaplan-Meier method. Results: Thirty-two glioblastoma cases with positive COVID-19 testing were matched to 64 glioblastoma controls with negative testing; age, sex, and molecular profiles did not differ between groups. Progression events occurred in 27 cases (84%) and 46 controls (72%). Of these, 14 cases (52%) presented with multifocal disease or leptomeningeal disease at progression compared with 10 controls (22%; P = .0082). Hyperprogression was identified in 13 cases (48%) but only 4 controls (9%; P = .0001). Cases had disease progression at a median of 35 days following COVID-19 testing, compared with 164 days for controls (P = .0001). Median survival from COVID-19 testing until death was 8.3 months for cases but 17 months for controls (P = .0016). Median overall survival from glioblastoma diagnosis was 20.7 months for cases and 24.6 months for controls (P = .672). Conclusions: Patients with glioblastoma may have accelerated disease progression in the first 2 months after COVID-19 infection. Infected patients should be monitored vigilantly. Future investigations should explore tumor-immune microenvironment changes linking tumor progression and COVID-19.

6.
Front Immunol ; 15: 1447021, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39247203

RESUMO

Immune checkpoint inhibitors (ICIs) reinvigorate anti-tumor immune responses by disrupting co-inhibitory immune checkpoint molecules such as programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4). Although ICIs have had unprecedented success and have become the standard of care for many cancers, they are often accompanied by off-target inflammation that can occur in any organ system. These immune related adverse events (irAEs) often require steroid use and/or cessation of ICI therapy, which can both lead to cancer progression. Although irAEs are common, the detailed molecular and immune mechanisms underlying their development are still elusive. To further our understanding of irAEs and develop effective treatment options, there is pressing need for preclinical models recapitulating the clinical settings. In this review, we describe current preclinical models and immune implications of ICI-induced skin toxicities, colitis, neurological and endocrine toxicities, pneumonitis, arthritis, and myocarditis along with their management.


Assuntos
Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Animais , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Colite/induzido quimicamente , Colite/imunologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Imunoterapia/efeitos adversos , Imunoterapia/métodos
7.
Nat Commun ; 13(1): 1970, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35413951

RESUMO

Immune checkpoint inhibitors are associated with immune-related adverse events (irAEs), including arthritis (arthritis-irAE). Management of arthritis-irAE is challenging because immunomodulatory therapy for arthritis should not impede antitumor immunity. Understanding of the mechanisms of arthritis-irAE is critical to overcome this challenge, but the pathophysiology remains unknown. Here, we comprehensively analyze peripheral blood and/or synovial fluid samples from 20 patients with arthritis-irAE, and unmask a prominent Th1-CD8+ T cell axis in both blood and inflamed joints. CX3CR1hi CD8+ T cells in blood and CXCR3hi CD8+ T cells in synovial fluid, the most clonally expanded T cells, significantly share TCR repertoires. The migration of blood CX3CR1hi CD8+ T cells into joints is possibly mediated by CXCL9/10/11/16 expressed by myeloid cells. Furthermore, arthritis after combined CTLA-4 and PD-1 inhibitor therapy preferentially has enhanced Th17 and transient Th1/Th17 cell signatures. Our data provide insights into the mechanisms, predictive biomarkers, and therapeutic targets for arthritis-irAE.


Assuntos
Artrite , Neoplasias , Artrite/induzido quimicamente , Artrite/tratamento farmacológico , Linfócitos T CD8-Positivos , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunoterapia/efeitos adversos , Neoplasias/tratamento farmacológico , Neoplasias/etiologia
9.
Curr Oncol Rep ; 10(1): 78-85, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18366964

RESUMO

Spinal cord compression (SCC) is a well-known complication in cancer patients, with an enormous potential impact on quality of life. In most cases, treatment is palliative, but a prompt diagnosis and immediate treatment is essential to preserving neurological function. Whereas steroids and radiation have been the mainstay of therapy for many years, the role and timing of surgery has remained controversial. However, class I evidence now exists to support the benefit of pre-irradiation surgical decompression in a carefully selected subpopulation of patients with SCC. A multidisciplinary approach is required to maximize the therapeutic and functional outcome of these patients.


Assuntos
Neoplasias/complicações , Compressão da Medula Espinal/diagnóstico , Compressão da Medula Espinal/terapia , Humanos , Compressão da Medula Espinal/etiologia
10.
Clin Cancer Res ; 13(23): 7133-8, 2007 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-18056194

RESUMO

PURPOSE: To determine the maximum tolerated dose of irinotecan when administrated with temozolomide every 28 days, in patients with recurrent malignant glioma who were also receiving CYP450 enzyme-inducing antiepileptic drugs (EIAED), and to characterize the pharmacokinetics of irinotecan and its metabolites. The study was also intended to assess whether temozolomide affects the conversion of irinotecan to SN-38. DESIGN: Patients with recurrent malignant glioma received a fixed dose of temozolomide (150 mg/m(2)) daily for 5 days from days 1 to 5 every 28 days, and an i.v. infusion of irinotecan on days 1 and 15 of each cycle. The starting dose of irinotecan was 350 mg/m(2), which was escalated to 550 mg/m(2) in 50-mg/m(2) increments. The plasma pharmacokinetics of irinotecan and its active metabolite, SN-38, were determined during the infusion of irinotecan on cycle 1, day 1. RESULTS: Thirty-three patients were enrolled into the study and treated. Thirty-one patients were evaluable for both tumor response and toxicity and two patients were evaluable for toxicity only. Common toxicities included neutropenia and thrombocytopenia, nausea, vomiting, and diarrhea. Dose-limiting toxicities were grade 3 diarrhea and nausea/vomiting. The maximum tolerated dose for irinotecan was determined to be 500 mg/m(2). CONCLUSIONS: The recommended phase II dose of irinotecan in combination with temozolomide for patients receiving EIAEDs is 500 mg/m(2), administrated every 15 days on a 28-day schedule. This study also confirmed that concomitant administration of EIAEDs increases irinotecan clearance and influences SN-38 disposition. No pharmacokinetic interaction was observed between temozolomide and irinotecan.


Assuntos
Anticonvulsivantes/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Neoplasias Encefálicas/metabolismo , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Camptotecina/farmacocinética , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Dacarbazina/análogos & derivados , Esquema de Medicação , Interações Medicamentosas , Indução Enzimática , Feminino , Glioma/metabolismo , Humanos , Irinotecano , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/metabolismo , Temozolomida
11.
Nat Rev Clin Oncol ; 15(1): 47-62, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28925994

RESUMO

Immunotherapy using T cells genetically engineered to express a chimeric antigen receptor (CAR) is rapidly emerging as a promising new treatment for haematological and non-haematological malignancies. CAR-T-cell therapy can induce rapid and durable clinical responses, but is associated with unique acute toxicities, which can be severe or even fatal. Cytokine-release syndrome (CRS), the most commonly observed toxicity, can range in severity from low-grade constitutional symptoms to a high-grade syndrome associated with life-threatening multiorgan dysfunction; rarely, severe CRS can evolve into fulminant haemophagocytic lymphohistiocytosis (HLH). Neurotoxicity, termed CAR-T-cell-related encephalopathy syndrome (CRES), is the second most-common adverse event, and can occur concurrently with or after CRS. Intensive monitoring and prompt management of toxicities is essential to minimize the morbidity and mortality associated with this potentially curative therapeutic approach; however, algorithms for accurate and consistent grading and management of the toxicities are lacking. To address this unmet need, we formed a CAR-T-cell-therapy-associated TOXicity (CARTOX) Working Group, comprising investigators from multiple institutions and medical disciplines who have experience in treating patients with various CAR-T-cell therapy products. Herein, we describe the multidisciplinary approach adopted at our institutions, and provide recommendations for monitoring, grading, and managing the acute toxicities that can occur in patients treated with CAR-T-cell therapy.


Assuntos
Imunoterapia Adotiva/efeitos adversos , Receptores de Antígenos de Linfócitos T/imunologia , Adulto , Encefalopatias/etiologia , Encefalopatias/terapia , Citocinas/metabolismo , Feminino , Humanos , Receptores de Antígenos de Linfócitos T/uso terapêutico , Síndrome
12.
J Clin Oncol ; 33(15): 1653-9, 2015 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-25897156

RESUMO

PURPOSE: Neurotoxic effects of brain irradiation include cognitive impairment in 50% to 90% of patients. Prior studies have suggested that donepezil, a neurotransmitter modulator, may improve cognitive function. PATIENTS AND METHODS: A total of 198 adult brain tumor survivors ≥ 6 months after partial- or whole-brain irradiation were randomly assigned to receive a single daily dose (5 mg for 6 weeks, 10 mg for 18 weeks) of donepezil or placebo. A cognitive test battery assessing memory, attention, language, visuomotor, verbal fluency, and executive functions was administered before random assignment and at 12 and 24 weeks. A cognitive composite score (primary outcome) and individual cognitive domains were evaluated. RESULTS: Of this mostly middle-age, married, non-Hispanic white sample, 66% had primary brain tumors, 27% had brain metastases, and 8% underwent prophylactic cranial irradiation. After 24 weeks of treatment, the composite scores did not differ significantly between groups (P = .48); however, significant differences favoring donepezil were observed for memory (recognition, P = .027; discrimination, P = .007) and motor speed and dexterity (P = .016). Significant interactions between pretreatment cognitive function and treatment were found for cognitive composite (P = .01), immediate recall (P = .05), delayed recall (P = .004), attention (P = .01), visuomotor skills (P = .02), and motor speed and dexterity (P < .001), with the benefits of donepezil greater for those who were more cognitively impaired before study treatment. CONCLUSION: Treatment with donepezil did not significantly improve the overall composite score, but it did result in modest improvements in several cognitive functions, especially among patients with greater pretreatment impairments.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Transtornos Cognitivos/tratamento farmacológico , Indanos/uso terapêutico , Piperidinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Colinesterase/uso terapêutico , Transtornos Cognitivos/etiologia , Terapia Combinada , Donepezila , Método Duplo-Cego , Feminino , Humanos , Aprendizagem/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Pessoa de Meia-Idade , Metástase Neoplásica , Testes Neuropsicológicos , Resultado do Tratamento , Adulto Jovem
13.
Neuro Oncol ; 17(2): 266-73, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25239666

RESUMO

BACKGROUND: Chemoradiation, followed by adjuvant temozolomide, is the standard treatment for newly diagnosed glioblastoma. Adding other active agents may enhance treatment efficacy. METHODS: The primary objective of this factorial phase II study was to determine if one of 3 potential chemotherapy agents added to dose-dense temozolomide (ddTMZ) improves progression-free survival (PFS) for patients with newly diagnosed glioblastoma. A prior phase I trial established the safety of combining ddTMZ with isotretinoin, celecoxib, and/or thalidomide. Adults with good performance status and no evidence of progression post chemoradiation were randomized into 8 arms: ddTMZ alone (7 days on/7 days off) or doublet, triplet, and quadruplet combinations with isotretinoin, celecoxib, and thalidomide. RESULTS: The study enrolled 155 participants with a median age of 53 years (range, 18-84 y). None of the agents demonstrated improved PFS when compared with arms not containing that specific agent. There was no difference in PFS for triplet compared with doublet regimens, although a trend for improved overall survival (OS) was seen (20.1 vs 17.0 months, P = .15). Compared with ddTMZ, the ddTMZ + isotretinoin doublet had worse PFS (10.5 vs 6.5 months, P = .043) and OS (21.2 vs 11.7 months, P = .037). Trends were also seen for worse outcomes with isotretinoin-containing regimens, but there was no impact with celecoxib or thalidomide combinations. Treatment was well tolerated with expected high rates of lymphopenia. CONCLUSIONS: The results do not establish a benefit for these combinations but indicate that adding isotretinoin to ddTMZ may be detrimental. This study demonstrated the feasibility and utility of the factorial design in efficiently testing drug combinations in newly diagnosed glioblastoma. CLINICALTRIALSGOV IDENTIFIER: NCT00112502.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Dacarbazina/análogos & derivados , Glioblastoma/tratamento farmacológico , Isotretinoína/uso terapêutico , Pirazóis/uso terapêutico , Sulfonamidas/uso terapêutico , Talidomida/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Celecoxib , Quimioterapia Adjuvante , Dacarbazina/administração & dosagem , Dacarbazina/uso terapêutico , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Humanos , Isotretinoína/administração & dosagem , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pirazóis/administração & dosagem , Sulfonamidas/administração & dosagem , Temozolomida , Talidomida/administração & dosagem , Adulto Jovem
14.
J Neurol ; 261(8): 1559-64, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24859329

RESUMO

Astrocytic tumors, especially optic pathway pilocytic astrocytomas, are common in pediatric NF1 patients. High-grade gliomas (HGGs) appear to be rare in adult and pediatric NF1 patients. This is a series of five consecutive, adult NF1 patients with recurrent HGGs treated at The University of Texas MD Anderson Cancer Center. Four patients met consensus clinical criteria for NF1 and one patient had presumed segmental NF1. Three patients had glioblastomas, one gliosarcoma, and one progressive, enhancing optic pathway glioma which was not biopsied. Two tumors had molecular testing performed; both were IDH wild type and activating oncogene mutations (1 BRAFV600E and 1 PIK3CA mutation) were found in these tumors. All five patients received bevacizumab-containing regimens at tumor recurrence. The median number of 4-week cycles of bevacizumab was 20. All five patients experienced prolonged post-recurrence survival following bevacizumab treatment ranging from ten to 72 months. The median overall survival from HGG diagnosis was 72.6 months with three patients alive and progression free at last follow-up. Three out of five patients developed vascular complications leading to bevacizumab discontinuation. In this case series, adult NF1 patients with recurrent HGGs had prolonged, post-recurrence survival after treatment with bevacizumab-containing regimens. Based on these results, further study of antiangiogenic therapy in NF1 patients with HGGs and bevacizumab-response in sporadic HGG patients with NF1-mutated tumors is warranted.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias Encefálicas , Glioma , Neurofibromatose 1 , Adulto , Bevacizumab , Encéfalo/patologia , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/mortalidade , Feminino , Seguimentos , Glioma/complicações , Glioma/tratamento farmacológico , Glioma/mortalidade , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neurofibromatose 1/complicações , Neurofibromatose 1/tratamento farmacológico , Neurofibromatose 1/mortalidade , Análise de Sobrevida
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