RESUMO
Several studies through the years have proven how an unhealthy nutrition, physical inactivity, sedentary lifestyle, obesity, and smoking represent relevant risk factors in cancer genesis. This study aims to provide an overview about the relationship between meningiomas and food assumption in the Mediterranean diet and whether it can be useful in meningioma prevention or it, somehow, can prevent their recurrence. The authors performed a wide literature search in PubMed and Scopus databases investigating the presence of a correlation between Mediterranean diet and meningiomas. The following MeSH and free text terms were used: "Meningiomas" AND "Diet" and "Brain tumors" AND "diet." Databases' search yielded a total of 749 articles. After duplicate removal, an abstract screening according to the eligibility criteria has been performed and 40 articles were selected. Thirty-one articles were excluded because they do not meet the inclusion criteria. Finally, a total of 9 articles were included in this review. It is widely established the key and protective role that a healthy lifestyle and a balanced diet can have against tumorigenesis. Nevertheless, studies focusing exclusively on the Mediterranean diet are still lacking. Thus, multicentric and/or prospective, randomized studies are mandatory to better assess and determine the impact of food assumptions in meningioma involvement.
Assuntos
Neoplasias Encefálicas , Dieta Mediterrânea , Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/prevenção & controle , Estudos Prospectivos , Neoplasias Meníngeas/prevenção & controleRESUMO
BACKGROUND: Meningiomas are one of the most common benign primary brain tumors; however, there is a paucity of literature on potential preventability. This comprehensive review aimed to explore the existing evidence for the potential risk factors that may contribute to meningioma development and to discuss early prevention strategies. METHODS: Literature search was conducted via MEDLINE, Embase, Web of Science, and Cochrane Database to retrieve existing literature on various environmental exposures and lifestyle behaviors that are potential risk factors for the development of meningiomas. RESULTS: Significant risk factors included exposure to ionizing radiation and certain environmental chemicals. Notably, this study also identified that cigarette smoking and obesity are associated with the development of meningiomas. To date, wireless phone usage, hormonal exposures, dietary factors, and traumatic brain injury remain inconclusive. Early prevention strategies should primarily be family-driven, community-based, and public health-endorsed strategies. Targeting unhealthy behaviors through healthcare organizations could execute a pivotal role in the maintenance of an optimum lifestyle, reducing the development of risk factors pertinent to meningiomas. CONCLUSIONS: To our knowledge, this is the first study that offers a perspective on prevention of meningiomas. A causal relationship of risk factors in developing meningiomas cannot be directly established with the current evidence. We are aware of the limitations of the hypothesis, but we believe that this study will raise more awareness and our findings could potentially be endorsed by organizations promoting health across the globe. Further prospective and retrospective studies will shed more light on this topic and help establish a definitive relationship.
Assuntos
Neoplasias Encefálicas , Neoplasias Meníngeas , Meningioma , Humanos , Meningioma/etiologia , Meningioma/prevenção & controle , Meningioma/patologia , Estudos Retrospectivos , Neoplasias Encefálicas/complicações , Fatores de Risco , Neoplasias Meníngeas/epidemiologia , Neoplasias Meníngeas/etiologia , Neoplasias Meníngeas/prevenção & controleRESUMO
BACKGROUND: Leptomeningeal metastasis (LM) is a severe complication of advanced non-small cell lung cancer (NSCLC). This retrospective study aimed to investigate the potential use of osimertinib for preventing LM in patients with advanced epidermal growth factor receptor (EGFR)-mutated NSCLC. METHODS: Patients with advanced NSCLC harboring EGFR mutations who underwent tyrosine kinase inhibitors (TKIs) therapy for at least 8 weeks between September 2016 and September 2019 were eligible for this study. All included patients were divided into two groups based on whether they received osimertinib, the osimertinib group (patients treated with osimertinib) and the control group (patients not treated with osimertinib). Propensity score matching (PSM, ratio of 1:1) was used to account for differences in baseline characteristics. The cumulative incidence of LM and the overall survival (OS) were evaluated. RESULTS: A total of 304 patients were included in the study population. Among them, 116 patients received osimertinib, and 188 did not. A total of 112 patients remained in each group after PSM, and the baseline characteristics were not significantly different between the two cohorts. LM developed in 11 patients (9.82%) in the osimertinib group and 24 patients (21.42%) in the control group (hazard ratio [HR] 0.38, 95% confidence interval [CI] 0.19-0.79, p = 0.009). Multivariate analysis indicated that osimertinib was an independent, statistically significant predictor for determining the risk for LM, with an HR of 0.33 (p = 0.042). At present, the OS rate data are too immature for statistical analysis. CONCLUSION: Real-world data demonstrate that osimertinib can significantly reduce the incidence of LM in patients with advanced NSCLC harboring common EGFR mutations. Given this result, osimertinib should be encouraged in clinical practice for specific patient populations.
Assuntos
Acrilamidas/uso terapêutico , Compostos de Anilina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Meníngeas/prevenção & controle , Neoplasias Meníngeas/secundário , Mutação , Acrilamidas/administração & dosagem , Acrilamidas/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina/administração & dosagem , Compostos de Anilina/efeitos adversos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Metástase Neoplásica , Pontuação de Propensão , Modelos de Riscos Proporcionais , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Epidemiological studies reported in 2016 and 2019 demonstrated that breast cancer patients under tamoxifen treatment had significantly reduced risks of meningioma development. Tamoxifen treatment duration longer than 1500 days or with cumulative dosage higher than 26 320 mg have especially lowered risk of meningioma. Clinical long-term anticancer efficacy of tamoxifen shall associate with simultaneous suppression of estrogen receptor and downregulation of certain growth factor pathways, which may associate with - but not limited to - protein kinase-C (PKC) signaling. In this study, we will put the evidence together and indicate that tamoxifen may be effective in meningioma treatment in some patients who do not express estrogen receptor but expresses PKC, yet much higher doses of tamoxifen will be needed to treat meningiomas than those applied to treat breast cancer. We underline the fact that immunohistochemical analysis of both estrogen receptor and PKC (especially α, δ, λ and ι isoenzymes) may guide in patient stratification for selective benefitting from tamoxifen in management of meningiomas. Lastly, it would also be logical to test individual responses of meningiomas to tamoxifen in primary monolayer and spheroid cultures before starting treatment in each patient as the differential distribution of PCK isoenzymes may cause also untoward effects.
Assuntos
Neoplasias da Mama , Neoplasias Meníngeas , Meningioma , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/prevenção & controle , Feminino , Humanos , Isoenzimas/uso terapêutico , Neoplasias Meníngeas/tratamento farmacológico , Neoplasias Meníngeas/epidemiologia , Neoplasias Meníngeas/prevenção & controle , Meningioma/tratamento farmacológico , Meningioma/epidemiologia , Meningioma/prevenção & controle , Receptores de Estrogênio/metabolismo , Tamoxifeno/uso terapêuticoRESUMO
OBJECTIVE: Glioma and meningioma are the most common primary brain tumors in adults. Epidemiologic studies of the relationship between female hormone exposure and exogenous hormone use and the risk of meningioma and glioma in females have yielded inconsistent results. METHODS: Two investigators comprehensively searched 3 electronic databases, including PubMed, Embase, and Cochrane Library. A total of 11 case-control studies were enrolled for meta-analysis. Dose-response meta-analyses were conducted. RESULTS: Compared with the non-oral contraceptives (OCs) female users, the female OC users might have reduced risk of glioma (risk ratio [RR], 0.87; 95% confidence interval [CI], 0.77-0.97; I2 = 42.6%). However, there was no obvious evidence of an association between OC use and the risk of meningioma in females (RR, 0.99; 95% CI, 0.87-1.13; I2 = 42.7%). Using OCs for >10 years in females may significantly decrease the risk of glioma to 30% (RR, 0.7; 95% CI, 0.6-0.81; I2 = 0%). The dose-response meta-analyses indicated that the risk of glioma in females significantly decreased when the duration of oral OC use was >7.5 years. CONCLUSIONS: OC use may not increase the risks of glioma and meningioma in females. Instead, the long-term use of OCs may significantly decrease the risk of glioma, and the benefits are even more pronounced when the time window is >7.5 years. Nonetheless, the pooled results in this study suggest that OC use may not increase the risk of meningioma. Therefore, our conclusion should be validated and supplemented in future larger studies.
Assuntos
Neoplasias Encefálicas/epidemiologia , Anticoncepcionais Orais/administração & dosagem , Glioma/epidemiologia , Neoplasias Meníngeas/epidemiologia , Meningioma/epidemiologia , Neoplasias Encefálicas/induzido quimicamente , Neoplasias Encefálicas/prevenção & controle , Estudos de Casos e Controles , Anticoncepcionais Orais/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Glioma/induzido quimicamente , Glioma/prevenção & controle , Humanos , Neoplasias Meníngeas/induzido quimicamente , Neoplasias Meníngeas/prevenção & controle , Meningioma/induzido quimicamente , Meningioma/prevenção & controle , Fatores de RiscoRESUMO
Previous studies suggest that hormone therapy may play an important role in the development of meningioma. However, it is unclear whether medication with tamoxifen can prevent meningioma. Our study cohort included all women who were diagnosed with breast cancer between 1961 and 2010, and a total of 227 535 women were identified with breast cancer with a median age at diagnosis of 63 years. Women diagnosed with breast cancer after 1987 were defined as tamoxifen exposed; those diagnosed with breast cancer before or during 1987 were defined as not exposed to tamoxifen. Standardized incidence ratios (SIRs) were used to calculate the risk of subsequent meningioma. Of these women, 223 developed meningioma. For women without tamoxifen exposure, the risk of meningioma was significantly increased, with an SIR of 1.54 (95% confidence interval 1.30-1.81); the risk was not increased in those with tamoxifen exposure (SIR=1.06, 95% confidence interval 0.84-1.32). The increased risk of meningioma in women without tamoxifen exposure persisted during 10 years of follow-up. In this historical cohort study, we found that women diagnosed with breast cancer but not treated with tamoxifen had an increased incidence of meningioma, whereas the incidence was close to that of the general population in patients treated with tamoxifen. This suggests that tamoxifen may prevent the development of meningioma.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias Meníngeas/prevenção & controle , Meningioma/prevenção & controle , Tamoxifeno/uso terapêutico , Idoso , Neoplasias da Mama/patologia , Feminino , Seguimentos , Humanos , Incidência , Neoplasias Meníngeas/epidemiologia , Neoplasias Meníngeas/patologia , Meningioma/epidemiologia , Meningioma/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Medição de Risco , Suécia/epidemiologiaRESUMO
PURPOSE: The relationship between hormone replacement therapy (HRT) and the incidence of meningioma in women has been investigated in several epidemiologic studies, but their results were not entirely consistent. Here, we performed a meta-analysis of case-control and cohort studies to analyze this association. METHODS: The PubMed database was searched from inception to 30 September 2012 to identify relevant studies that met pre-stated inclusion criteria. We also reviewed reference lists from the retrieved articles. Two researchers evaluated study eligibility and extracted the data independently. Odds ratios (ORs) or relative risks and 95 % confidence intervals (CIs) were extracted and pooled using the fixed-effect or random-effects models. RESULTS: A total of 11 studies (six case-control and five cohort studies) were included in this meta-analysis, involving 1,820,954 participants, of whom 3,249 had meningioma. When compared to never users of HRT, the pooled OR with ever users for meningioma was 1.29 (95 % CI 1.03-1.60). Sensitivity analyses restricted to postmenopausal women yielded similar results (OR: 1.22; 95 % CI 1.02-1.46). Subgroup analyses showed that the pooled ORs were 1.27 (95 % CI 1.08-1.49, p < 0.05) and 1.12 (95 % CI 0.95-1.32) for current and past users of HRT, respectively. CONCLUSION: Hormone replacement therapy use is associated with an increased risk of meningioma in women, as well as in postmenopausal women. Besides, the significant risk elevation is present in current users but not in past users. Future research should attempt to establish whether this association is causal and to clarify its mechanisms.
Assuntos
Terapia de Reposição Hormonal/efeitos adversos , Neoplasias Meníngeas/induzido quimicamente , Meningioma/induzido quimicamente , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Neoplasias Meníngeas/prevenção & controle , Meningioma/prevenção & controle , Fatores de RiscoRESUMO
BACKGROUND: CD163 is a 130-kDa transmembrane protein expressed in human monocytes and macrophages, and the aberrant expression of CD163 in breast and colorectal cancer associated with patients' poor prognosis was reported. Here, we analyzed the expression of CD163 in meningioma, a common intracranial tumor, and its molecular mechanism in association with meningioma progression. METHODS: First, we performed immunohistochemical analysis using 50 human meningioma specimens. Next, we established CD163-overexpressing human meningioma cell lines and investigated its roles in tumor progression in vitro and in vivo. RESULTS: Immunohistochemically, 26 of 50 human meningioma specimens (52.0%) were positive for CD163 in tumor cells, including benign grade I (48.5%) and grade II (71.4%) cases. Furthermore, CD163 expression was correlated with histological atypical parameters that directly predict the prognosis of meningioma. CD163-overexpressing meningioma cells showed significant suppression of apoptosis and accelerated tumor growth in nude mice. In addition, unexpected splenomegaly affiliated with the xenograft predicted tumor-derived granulocyte colony-stimulating factor (G-CSF) production, which was confirmed by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay. CONCLUSIONS: To our knowledge, this is the first report that demonstrates CD163 expression in meningioma not only by immunohistochemistry but also by reverse-transcription polymerase chain reaction, using primary culture cells, and provides the novel molecular function of CD163 to prevent apoptosis through the production of G-CSF in meningioma.
Assuntos
Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Apoptose , Proliferação de Células , Fator Estimulador de Colônias de Granulócitos/metabolismo , Neoplasias Meníngeas/prevenção & controle , Meningioma/patologia , Receptores de Superfície Celular/metabolismo , Adulto , Idoso , Animais , Antígenos CD/genética , Antígenos de Diferenciação Mielomonocítica/genética , Western Blotting , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patologia , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Gradação de Tumores , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Superfície Celular/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Adulto JovemRESUMO
PURPOSE: To evaluate the mTORC1 (mammalian target of rapamycin complex 1) pathway in meningiomas and to explore mTORC1 as a therapeutic target in meningioma cell lines and mouse models. EXPERIMENTAL DESIGN: Tissue microarrays (53 meningiomas of all WHO grades) were stained for phosphorylated polypeptides of mTOR, Akt, and the mTORC1 targets 4EBP1 and p70S6K, the latter being the consensus marker for mTORC1 activity. Expression of proteins and mRNAs was assessed by Western blotting and real-time PCR in 25 tumors. Cell lines Ben-Men-1 (benign), IOMM-Lee and KT21 (malignant), and pairs of merlin-positive or -negative meningioma cells were used to assess sensitivity toward mTORC1 inhibitors in methyl-tetrazolium and bromodeoxyuridine (BrdUrd) assays. The effect of temsirolimus (20 mg/kg daily) on tumor weight or MRI-estimated tumor volume was tested by treatment of eight nude mice (vs. 7 controls) carrying subcutaneous IOMM-Lee xenografts, or of eight (5) mice xenotransplanted intracranially with IOMM-Lee (KT21) cells in comparison to eight (5) untreated controls. RESULTS: All components of the mTORC1 pathway were expressed and activated in meningiomas, independent of their WHO grade. A significant dosage-dependent growth inhibition by temsirolimus and everolimus was observed in all cell lines. It was slightly diminished by merlin loss. In the orthotopic and subcutaneous xenograft models, temsirolimus treatment resulted in about 70% growth reduction of tumors (P < 0.01), which was paralleled by reduction of Ki67 mitotic index (P < 0.05) and reduction of mTORC1 activity (p70S6K phosphorylation) within the tumors. CONCLUSION: mTORC1 inhibitors suppress meningioma growth in mouse models, although the present study did not measure survival.
Assuntos
Modelos Animais de Doenças , Neoplasias Meníngeas/prevenção & controle , Meningioma/prevenção & controle , Complexos Multiproteicos/antagonistas & inibidores , Sirolimo/análogos & derivados , Serina-Treonina Quinases TOR/antagonistas & inibidores , Animais , Apoptose , Western Blotting , Adesão Celular , Proliferação de Células , Genes da Neurofibromatose 2/fisiologia , Humanos , Técnicas Imunoenzimáticas , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina , Neoplasias Meníngeas/metabolismo , Neoplasias Meníngeas/patologia , Meningioma/metabolismo , Meningioma/patologia , Camundongos , Camundongos Nus , Complexos Multiproteicos/genética , Complexos Multiproteicos/metabolismo , Gradação de Tumores , Inibidores de Proteínas Quinases/farmacologia , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Células Tumorais CultivadasRESUMO
OBJECTIVE: To introduce a kind of method for skull base reconstruction after resecting anterior skull base tumors involving paranasal sinuses. METHOD: A retrospective analysis was carried out on 13 patients who underwent anterior skull base reconstruction. Pericranial flap were detached with integrity from the frontal bone during craniotomy, after the tumor had been resected partitionedly, the cribriform plate of ethmoid bone which was involved by tumor was resected. Using the fat tissue to fill the skull-base defects and sutured the pedicled pericranial flap with surrounding normal dura mater. Then reinforced at the junction of pericranial flap and dura mater with biogel. RESULT: The pathogenic diagnosis of all cases were meningioma. I grade resection was acquired in 12 cases and II grade in 1 case according to Simpson grading standard of meningioma resection. The postoperative complications were 3 cases aseptic meningitis, 3 cases frontal syndrome. No CSF leakage, intracranial infection, nor death occurred. An average of 3. 4-year follow-up was achieved in all the cases from 9 months to 8 years, no tumor relapse. CONCLUSION: CSF leakage can be effectively prevented by filling the skull-base defects with the fat tissue, suturing the pedicled pericranial flap with surrounding normal dura mater, and reinforcing at the junction of pericranial flap and dura mater with biogel.
Assuntos
Rinorreia de Líquido Cefalorraquidiano/prevenção & controle , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Neoplasias da Base do Crânio/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Neoplasias Meníngeas/prevenção & controle , Meningioma/patologia , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/métodos , Estudos Retrospectivos , Base do Crânio/cirurgia , Neoplasias da Base do Crânio/patologiaRESUMO
BACKGROUND AND PURPOSE: Some CNS tumours present leptomeningeal dissemination. Craniospinal radiotherapy is complex and recurrences may occur at sites of target volume underdosage. IMRT, being highly conformal to the target, could theoretically underdose the optic nerves if they are not specifically targeted leading to optic nerve recurrences. We analyzed optic nerve dosimetry when they are not specifically targeted. MATERIALS AND METHODS: We designed 3D-conformal and tomotherapy plans for our last five patients treated to the craniospinal axis, not including the optic nerves in the target volume. We analyzed the dose delivered to the optic nerves, to the anterior and posterior half of the optic nerves, and to a theoretical optic nerve-PTV. RESULTS: The dose delivered to the optic nerves was similar for both plans in all patients (V95% close to 100%) except one in whom tomotherapy considerably underdosed the anterior optic nerves. The dose to the optic nerve-PTV was lower with tomotherapy in all patients. CONCLUSION: Despite not intentionally targeting the optic nerves, the dose to the optic nerves with IMRT was similar to 3D-conformal plans in most cases but left no margin for setup error. In individual cases the anterior half of the optic nerves could be significantly underdosed.
Assuntos
Neoplasias do Sistema Nervoso Central/radioterapia , Irradiação Craniana , Nervo Óptico/efeitos da radiação , Radioterapia de Intensidade Modulada , Neoplasias do Sistema Nervoso Central/patologia , Humanos , Neoplasias Meníngeas/prevenção & controle , Neoplasias Meníngeas/secundário , Meninges/efeitos da radiação , Dosagem Radioterapêutica , Radioterapia Conformacional , Medula Espinal/efeitos da radiaçãoRESUMO
Central nervous system (CNS) recurrence continues to be a significant complication in the treatment of adult patients with acute lymphoblastic leukemia (ALL). Preventing CNS recurrence has been a therapeutic challenge and has not been addressed critically in many clinical trials. Adult studies modeled on childhood ALL studies have used multiple treatment modalities, including radiation therapy, systemic therapy, intrathecal therapy, and combinations thereof. Cranial irradiation is effective but is offset by substantial toxicity, including neurologic sequelae. Systemic chemotherapy, especially with cytarabine (AraC) and methotrexate, has demonstrated promise in decreasing CNS recurrence, but therapeutic levels of drugs in the cerebrospinal fluid (CSF) are not maintained. Intrathecal chemotherapy with or without high-dose systemic therapy is the most common approach to CNS prophylaxis. Liposomal AraC recently has become available and confers prolonged levels of free AraC in the CSF, a critical requirement for CNS prophylactic therapy. This review discusses the various modalities used for CNS prophylaxis in patients with ALL and the emerging trends, with specific emphasis on the outcome in terms of event-free survival and toxicity.
Assuntos
Sistema Nervoso Central/patologia , Infiltração Leucêmica/prevenção & controle , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Irradiação Craniana , Humanos , Injeções Espinhais , Carcinomatose Meníngea/prevenção & controle , Neoplasias Meníngeas/prevenção & controle , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , RecidivaRESUMO
We report a case of a 57-year-old African American male patient with standard risk (IIIA) IgA kappa multiple myeloma. This patient presented with neurologic complaints (manifesting as generalized muscle weakness and swallowing dysfunction associated with a poor cough reflex) 10 months after achieving a very good partial remission and without evidence of systemic progression. Examination of the cerebrospinal fluid revealed leptomeningeal involvement. Very little is known about the mechanisms of myelomatous spread to the leptomeninges, a very rare event, and the presentation of this case could raise awareness of this rare complication in those involved in caring for patients with multiple myeloma.
Assuntos
Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/etiologia , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Diagnóstico Diferencial , Humanos , Masculino , Neoplasias Meníngeas/prevenção & controle , Pessoa de Meia-Idade , Prevenção SecundáriaRESUMO
The current WHO 2007 classification divides meningiomas into a 3-grade prognostic hierarchy. Recent literature evokes two pathways to disease progression in meningiomas akin to a comparable paradigm in gliomas, but without similar prognostic connotation: de novo anaplastic meningioma (better prognosis), and transformed meningioma (worse prognosis). We present two adult cases of transformed meningiomas that display a spectrum of morphologic progression. Case 1 at presentation showed a random admixture of meningothelial, atypical and anaplastic meningioma. The tumor recurred as anaplastic meningioma. Case 2 presented as a chordoid meningioma, but recurred as anaplastic meningioma mainly at the invasive front in transition with residual chordoid pattern. Of interest, portions of tumor also showed papillary configuration. In accordance with the dire prognosis for anaplastic meningioma, both patients succumbed to their disease within 2 months of recurrence. The present study highlights two main points: First, that proper recognition of focal high-grade areas in a heterogeneous low-grade meningioma (case 1) provides critical morphologic clues to spatial histologic progression and predicts aggressive biologic behavior, as evidenced by progression to frankly anaplastic meningioma at recurrence. Second, the presence of papillary in addition to anaplastic areas, in the recurrence of a previously diagnosed chordoid meningioma supports the ostensibly heightened transforming potential of grade II meningiomas, but also reflects on the morphologic heterogeneity of high-grade meningiomas, and their potentially diverse pathways of progression. We propose that grading of meningiomas as outlined by WHO is of more critical prognostic import than histologic sub-typing, and must include a thorough survey of the tumor-brain interface. Future molecular genetic correlates, akin to those characterized in gliomas, could help stratify prognostic subcategories to refine meningioma grading, and govern optimal therapeutic strategies.
Assuntos
Neoplasias do Plexo Corióideo/diagnóstico , Neoplasias do Plexo Corióideo/patologia , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/patologia , Meningioma/diagnóstico , Meningioma/patologia , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Neoplasias do Plexo Corióideo/prevenção & controle , Diagnóstico Diferencial , Progressão da Doença , Evolução Fatal , Humanos , Masculino , Neoplasias Meníngeas/prevenção & controle , Meningioma/prevenção & controle , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , PrognósticoAssuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Crise Blástica , Criança , Pré-Escolar , Humanos , Injeções Espinhais , Neoplasias Meníngeas/prevenção & controle , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prednisona/uso terapêutico , Prognóstico , Fatores de RiscoAssuntos
Citarabina/administração & dosagem , Linfoma não Hodgkin/tratamento farmacológico , Neoplasias Meníngeas/prevenção & controle , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adulto , Idoso , Feminino , Humanos , Injeções Espinhais , Lipossomos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Somatostatin receptors, especially the sst2A subtype, are present on most meningiomas. The addition of somatostatin inhibits meningioma growth in vitro in some studies. There have been anecdotal reports of octreotide inhibiting growth in meningiomas. OBJECTIVES: A prospective pilot trial of sustained-release somatostatin (Sandostatin LAR) in 16 patients with recurrent meningiomas was conducted with a primary study objective of progression-free survival at 6 months. METHODS: Sixteen patients (11 women, 5 men; median age 58) with recurrent meningioma were treated prospectively with long-acting somatostatin. Patients had progressed radiographically after prior therapy with surgery (14/16; complete resection in 5; subtotal in 7; biopsy only in 2), radiotherapy (13/16), and chemotherapy (12/16). All patients had confirmation of the presence of somatostatin receptors in their tumor using (111)In-octreotide, a long-acting somatostatin agonist, SPECT scanning. RESULTS: Patients received 2 to 15 cycles (median 4.5) of somatostatin with minimal toxicity. Five [corrected] partial responses, five stable disease, and six [corrected] progressive disease patterns were seen. Duration of response ranged from 2 to 20+ months (median 5.0 months). Median survival was 7.5 months (range 3 to 20+). The overall progression-free survival was 44% (seven patients) at 6 months. CONCLUSIONS: In this small trial of patients with recurrent meningiomas shown to overexpress somatostatin receptors by octreotide scintigraphy, long-acting somatostatin (Sandostatin LAR) was administered on a monthly schedule. Thirty-one percent of patients demonstrated a partial radiographic response and 44% achieved progression-free survival at 6 months. Toxicity was minimal, suggesting somatostatin analogues may offer a novel, relatively nontoxic alternative treatment for recurrent meningiomas.
Assuntos
Neoplasias Meníngeas/tratamento farmacológico , Meningioma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Terapia de Salvação/métodos , Somatostatina/análogos & derivados , Somatostatina/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Preparações de Ação Retardada , Esquema de Medicação , Feminino , Humanos , Masculino , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/prevenção & controle , Meningioma/patologia , Meningioma/prevenção & controle , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/prevenção & controle , Projetos Piloto , Estudos Prospectivos , Somatostatina/químicaRESUMO
BACKGROUND: Treatments for recurrent meningiomas are limited. We previously demonstrated universal expression of COX-2 in meningiomas and dose-dependent growth inhibition in vitro with celecoxib, a COX-2 inhibitor. We therefore tested the effects of celecoxib on meningioma growth in a mouse xenograft model. METHODS: Meningioma cell lines (IOMM-Lee, CH157-MN, WHO grade I primary cultured tumor) were transplanted into flanks of nude mice fed mouse chow with celecoxib at varying concentrations (0, 500, 1000, 1500 ppm) ad libitum. Tumors were measured biweekly and processed for MIB-1, Factor VIII, COX-2, and VEGF, and assayed with transferase-mediated dUTP-biotin nick-end labeling (TUNEL). RESULTS: Celecoxib reduced growth of mean tumor volume by 66% (P < .05), 25% (P > .05), and 65% (P < .05) compared with untreated controls in IOMM-Lee, CH157-MN, and benign tumors, respectively. IOMM-Lee tumors removed from celecoxib treatment regained a growth rate similar to the control. Blood vessel density decreased and apoptotic cells increased in treated flank tumors. Diminished COX-2 expression and VEGF were observed in treated IOMM-Lee tumors. Mean plasma celecoxib levels were 845, 1540, and 2869 ng/mL, for low-, medium-, and high-dose celecoxib, respectively. CONCLUSIONS: Celecoxib inhibits meningioma growth in vivo at plasma levels achievable in humans. Celecoxib-treated tumors were less vascular with increased apoptosis. IOMM-Lee tumors treated with celecoxib showed decreased COX-2 and VEGF expression. COX-2 inhibitors may have a role in the treatment of recurrent meningiomas.
Assuntos
Inibidores de Ciclo-Oxigenase/uso terapêutico , Neoplasias Meníngeas/prevenção & controle , Meningioma/prevenção & controle , Pirazóis/uso terapêutico , Sulfonamidas/uso terapêutico , Animais , Apoptose , Celecoxib , Ciclo-Oxigenase 2/metabolismo , Fator VIII/metabolismo , Humanos , Técnicas Imunoenzimáticas , Marcação In Situ das Extremidades Cortadas , Antígeno Ki-67/metabolismo , Neoplasias Meníngeas/enzimologia , Neoplasias Meníngeas/patologia , Meningioma/enzimologia , Meningioma/patologia , Camundongos , Camundongos Nus , Taxa de Sobrevida , Células Tumorais Cultivadas , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Although CD20- relapses of B-cell lymphoma following rituximab therapy have increasingly been reported recently, coexistence of both the original and selected clones on relapse in a single patient have not been described. We experienced such a case with rare CD5+ intravascular lymphomatosis (IVL). A 46-year-old woman was admitted because of IVL complicated with cauda equina syndrome and pulmonary infarction. Complete remission was successfully achieved with multidrug chemotherapy in combination with rituximab. However, the disease recurred after 8 months with leukemic progression and meningeal involvement. The phenotype of the abnormal lymphocytes in the peripheral blood was fundamentally the same (CD20+CD5+CD10-CD19+CD23-sIglambda+) as that of the cells in the cerebrospinal fluid (CSF). However, CD20 expression was decreased remarkably compared with that in the CSF and that in the bone marrow before therapy. The targeting of CD20 molecules on the tumor cell surface by rituximab may have provided a selective pressure on lymphoma cells. The escape phenomenon of the lymphoma cells from rituximab was observed by simultaneously comparing the CD20 expression of cells in the peripheral blood and in a site of sanctuary from rituximab, the CSF.
Assuntos
Antígenos CD20 , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Antígenos CD5 , Linfoma de Células B/prevenção & controle , Neoplasias Meníngeas/prevenção & controle , Evasão Tumoral/efeitos dos fármacos , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Murinos , Antígenos CD20/líquido cefalorraquidiano , Antígenos CD5/líquido cefalorraquidiano , Feminino , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Humanos , Linfócitos/metabolismo , Linfócitos/patologia , Linfoma de Células B/líquido cefalorraquidiano , Linfoma de Células B/patologia , Neoplasias Meníngeas/líquido cefalorraquidiano , Neoplasias Meníngeas/patologia , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , RituximabRESUMO
PURPOSE: The toxicity and antitumor activity of regional intrathecal delivery of an oncolytic recombinant poliovirus, PVS-RIPO, was evaluated in rodent models of glioblastoma multiforme neoplastic meningitis. EXPERIMENTAL DESIGN: To evaluate for toxicity, PVS-RIPO was administered into the spinal cord of transgenic mice that express the human poliovirus receptor, CD155, and into the intrathecal space of athymic rats without tumor. To evaluate efficacy, two different doses of PVS-RIPO were administered intrathecally 3 days after athymic rats were inoculated intrathecally with an aggressive human glioblastoma multiforme xenograft. RESULTS: No clinical or histologic evidence of toxicity was found. In efficacy studies, median survival was increased by 174.47% from 8.5 days in the group treated with UV light-inactivated virus to 15 days in the rats treated with 1.0 x 10(7) plaque-forming units (pfu) of PVS-RIPO (P < 0.0001). A similar increase in median survival was seen in the group receiving 1.0 x 10(9) pfu PVS-RIPO (P < 0.0001); however, there was no statistically significant dose-response relationship (P = 0.345). In addition, 1 of 10 rats in lower-dose PVS-RIPO-treated group and 3 of 10 rats in higher-dose PVS-RIPO-treated group survived >60 days after tumor cell inoculation and had no evidence of residual tumor at autopsy. CONCLUSION: These results suggest that intrathecal treatment with PVS-RIPO may be useful for treatment of neoplastic meningitis in patients with glioblastoma multiforme and provides a rationale for clinical trials in this area.