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BACKGROUND: In the randomized phase II REGOMA trial, regorafenib showed promising activity in patients with recurrent glioblastoma. We conducted a large, multicenter, prospective, observational study to confirm the REGOMA data in a real-world setting. PATIENTS AND METHODS: The major inclusion criteria were histologically confirmed diagnosis of glioblastoma according to the World Health Organization (WHO) 2016 classification and relapse after radiotherapy with concurrent/adjuvant temozolomide treatment, good performance status [Eastern Cooperative Oncology Group performance status (ECOG PS 0-1)] and good liver function. Regorafenib was administered at the standard dose of 160 mg/day for 3 weeks on/1 week off. Brain magnetic resonance imaging was carried out within 14 days before starting regorafenib and every 8-12 weeks. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective response rate, disease control rate (DCR), safety and health-related quality of life. The Response Assessment in Neuro-Oncology (RANO) criteria were used for response evaluation and Common Terminology Criteria for Adverse Events (CTCAE) version 5 for assessment of adverse events (AEs). RESULTS: From September 2020 to October 2022, 190 patients with recurrent glioblastoma were enrolled from 30 cancer centers in Italy: their median age was 58.5 years [interquartile range (IQR) 53-67 years], 68% were male and 85 (44.7%) were in optimal clinical condition (ECOG PS 0). The number of patients taking steroids at baseline was 113 (60%); the second surgery was carried out in 39 (20.5%). O6-methylguanine-DNA methyltransferase (MGMT) was methylated in 80 patients (50.3%) and 147 (92.4%) of the patients analyzed had isocitrate dehydrogenase (IDH) wild type. The median follow-up period was 20 months (IQR 15.6-25.5 months). The median OS was 7.9 months ([95% confidence interval (CI) 6.5-9.2 months] and the median PFS was 2.6 months (95% CI 2.3-2.9 months). Radiological response was partial response and stable disease in 13 (7.3%) and 26 (14.6%) patients, respectively, with a DCR of 21.9%. The median number of regorafenib cycles per patient was 3 (IQR 2.0-4.0). Grade 3-4 drug-related adverse events were reported in 22.6% of patients. A dose reduction due to AEs was required in 36% of patients. No deaths were considered as treatment-related AEs. CONCLUSIONS: This large, real-world observational study showed similar OS with better tolerability of regorafenib in patients with relapsed glioblastoma compared with the REGOMA study.
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Neoplasias Encefálicas , Glioblastoma , Recurrencia Local de Neoplasia , Compuestos de Fenilurea , Piridinas , Humanos , Glioblastoma/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Piridinas/uso terapéutico , Piridinas/farmacología , Anciano , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/farmacología , Neoplasias Encefálicas/tratamiento farmacológico , Italia , Adulto , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Calidad de Vida , Resultado del TratamientoRESUMEN
OBJECTIVE: Peripherally inserted central catheters (PICC) guarantee a stable and safe vascular access to administer irritants or vesicants therapies. However, they may occasionally be affected by relevant thrombotic complications especially in patients with hypercoagulability such as oncological patients. Among the identification of independent risk factors, the role of body mass index (BMI) ≥25 kg/m2 is now emerging in literature with conflicting results. The aim of this systematic review is to analyze the available scientific literature in order to determine whether BMI could represent a risk factor in the development of thromboembolic event among cancer patients with PICCs. DATA SOURCES AND REVIEW METHODS: A scientific literature review was performed in Pubmed, Embase and Cinahl from Jan 1, 2010 to September 10, 2020 in which we identified 100 records. Of these, 88 were excluded and 14 were reviewed in full text. Among the reviewed records, 6 articles satisfied the inclusion criteria for analysis. These criteria included the English language, oncological patients with PICCs, the evaluation of catheter-related thrombosis as well as the stratification of patients according to BMI. Studies off topic and lacking data on PICC related complications among overweight and underweight patients were excluded. The includedstudies, judged with Newcastle-Ottawa Scale, was fair-lower quality. The primary endpoint was the relative risk (RR) of PICC-related thrombosis of overweight/obese vs normal weight/underweight (i.e., BMI ≥25 vs <25 kg/m2) in cancer patients. RESULTS: A total of 2431 patients were included in the analysis. Overall, 15.1% of patients developed PICC-related thrombosis within a median time of 23.2 days (range 11.0-42.5) after PICC implantation. Concerning BMI, 52.6% of the entire population was overweight/obese. We assessed the proportion of patients with PICC-related thrombotic events in the two groups, with 28% (95% CI, 12%-45%) of events registered in the overweight/obese patients cohort, and 13% (95% CI, 6%-19%) in the normal weight/underweight cohort. The pooled relative risk (RR) was 2.06 (95% CI, 1.21-3.49, p<0.001) in overweight/obese vs normal weight/underweight patients. CONCLUSION: This review showed a two-fold risk of thrombosis in overweight/obese compared to normal weight/underweight oncological patients with PICCs. Underweight condition could also play a role in thrombosis development, especially in nasopharyngeal and digestive system cancer. Future prospective studies are needed to achieve reliable results and produce useful conclusion.
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Cateterismo Venoso Central , Cateterismo Periférico , Neoplasias , Tromboembolia , Índice de Masa Corporal , Cateterismo Venoso Central/efectos adversos , Cateterismo Periférico/efectos adversos , Humanos , Neoplasias/complicaciones , Obesidad/complicaciones , Sobrepeso/etiología , Estudios Retrospectivos , Factores de Riesgo , Delgadez/etiología , Tromboembolia/etiologíaRESUMEN
INTRODUCTION: Meningiomas are usually considered benign lesions, however a proportion of them shows a more aggressive behavior, defined high-grade meningiomas (HGM). Effective medical treatments are lacking, especially at the time of recurrence. METHODS: Through a retrospective analysis, we examined epidemiological, diagnostic, therapeutic, recurrence information and survival data of HGM treated at our institution between 2010 and 2018. RESULTS: 183 patients (105 females and 78 males), with median age of 58 years (25-88), were included; 168 were atypical, 12 anaplastic, 3 rhabdoid. Overall, m-PFS was 4.2 years, and m-OS was 10.3 years. Gross-total resection had a 5-year survival rate of 95% compared with subtotal/partial resection (86% and 67%) (p = 0.002). Higher expression of Ki-67/MIB-1 seems associated with higher risk of death (HR:1.06 with 95% CI, 1.00-1.12, p = 0.03). No statistically significant differences were seen in survival between the group managed with a wait-and-see strategy vs the group treated with RT while a difference on PFS was seen (4.1 years vs 5.2 years p = 0.03). After second recurrence, the most employed treatments were systemic therapies with a very limited effect on disease control. CONCLUSIONS: Data confirmed the aggressive behavior of HGM. The extent of resection seems to correlate with a favorable outcome regardless histological subtypes. The role of RT remains controversial, with no statistically significant impact on OS but a possible role on PFS. Recurrent HGM remains the real challenge, to date no chemotherapies are able to achieve disease control. Future research should focus on biological/molecular predictors in order to achieve a patient-tailored treatment.
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Neoplasias Meníngeas/patología , Neoplasias Meníngeas/terapia , Meningioma/patología , Meningioma/terapia , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos/métodos , Radioterapia Adyuvante/métodos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: The use of central venous catheters with peripheral insertion (PICC) has increased rapidly in recent years, particularly in cancer patients. The benefits provided may occasionally be affected by relevant complications, such as infections and thrombotic events, especially in neuro-oncological patients. To date, the risk of PICC-related complications in this subset of patients is unknown, as is tolerability. As a primary objective, this study aimed to collect complications related to PICCs in primary neuro-oncological patients. As a secondary objective, the study aimed to evaluate PICC tolerability. METHODS: Neuro-oncological patients with PICCs that were placed as part of normal clinical practice at IRCCS Neurologico C. Besta were consecutively enrolled in the study. PICC-related complications were recorded immediately (during the procedure), early (within 1 week after PICC insertion), and late (1-3-5 months after PICC placement). At the same time points, all patients were also evaluated for tolerability through interviews with semi-structured, open-ended questions. RESULTS: Sixty patients were enrolled (41 males and 19 females, with a median age of 56.2 years). Excluding loss to follow-up, 33/49 patients developed at least one complication related to the PICC. Immediate complications mainly included hematoma (8), accidental arterial puncture (4), and primary malpositioning (3). Regarding early and late complications, 3 device-related infections, 8 thrombotic events, and 20 mechanical complications were registered. Semi-structured interviews revealed an overall positive experience with the device. The most negative impact was on hygiene habits, with 34 patients becoming caregiver-dependent. Over time, almost all patients became used to the device and perceived greater security during chemotherapy. A strongly negative issue was the difficulty of relying on competently trained healthcare personnel in outpatient setting. CONCLUSION: The results showed a nonnegligible increased thromboembolic risk in neuro-oncological patients with PICCs, almost double that in historical oncological populations. It is essential to extend the study to a greater number of patients to achieve reliable results and to identify patients at high risk. The device seems to be positively accepted by the majority of patients, without affecting activities of daily living.
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Infecciones Relacionadas con Catéteres/etiología , Adulto , Anciano , Anciano de 80 o más Años , Cateterismo Venoso Central/efectos adversos , Cateterismo Periférico/efectos adversos , Catéteres Venosos Centrales/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Extra-cranial metastases of glioblastoma (GBM) represent a rare event, and the biological-genetic mechanisms involved in the pathogenesis have not yet been determined. We report the case of a young patient with multiple visceral and osseous metastases occurred after 4 years after first diagnosis of GBM. The strangeness as well as the rarity of this event does not allow to identify an effective treatment for GBM metastases, making the management of this ominous tumor an even greater challenge.
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Neoplasias Encefálicas/patología , Glioblastoma/secundario , Adulto , Neoplasias Encefálicas/terapia , Diagnóstico Diferencial , Resultado Fatal , Glioblastoma/patología , Glioblastoma/terapia , Humanos , Masculino , Metástasis de la Neoplasia/diagnóstico por imagenRESUMEN
Oligodendrogliomas represent the third most common type of glioma, comprising 4%-15% of all gliomas and can be classified by degree of malignancy into grade II and grade III, according to WHO classification. Only 30% of oligodendroglial tumors have anaplastic characteristics. Anaplastic oligodendroglioma (AO) is often localized as a single lesion in the white matter and in the cortex, rarely in brainstem or spinal cord. The management of AO is deeply changed in the recent years. Maximal safe surgical resection followed by radiotherapy (RT) was considered as the standard of care since paramount findings regarding molecular aspects, in particular co-deletion of the short arm of chromosome 1 and the long arm of chromosome 19, revealed that these subsets of AO, benefit in terms of overall survival (OS) and progression-free survival (PFS), from the addition of chemotherapy to RT. Allelic losses of chromosomes 1p and 19q occur in 50%-70% of both low-grade and anaplastic tumors, representing a strong prognostic factor and a powerful predictor of prolonged survival. Several other molecular markers have potential clinical significance as IDH1 mutations, confirming the strong prognostic role for OS. Malignant brain tumors negatively impacts on patients' quality of life. Seizures, visual impairment, headache, and cognitive disorders can be present. Moreover, chemotherapy and RT have important side effects. For these reasons, "health-related quality of life" is becoming a topic of growing interest, investigating on physical, mental, emotional, and social well-being. Understanding the impact of medical treatment on health-related quality of life will probably have a growing effect both on health care strategies and on patients.
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The purpose of this study was to analyze the psychological well-being, quality of life, and cognitive strategies activated by patients with high-grade glioma. We hypothesized that the self-perceived quality of life is modulated by physical and psychological factors and that in order to understand this modulation more psychometric approaches are necessary. Data were collected from a sample of 73 consecutive patients with a histological diagnosis of primary malignant brain cancer (grade IV glioblastoma and grade III anaplastic astrocytoma) hospitalized in a specialized Italian center. The Functional Assessment of Cancer Therapy (FACT) scale and the Schedule of Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW) scale were used to assess quality of life. The mean FACT-Brain (Br) score was 122.37. Similarly, the median SEIQoL-DW score was 72.9 out of a maximum value of 100. No gender effect was found in relation to overall quality of life. Patients with high depression and/or anxiety scores reported lower quality of life (QoL) scores in all the instruments considered. We did not find any gender effect concerning depression and anxiety levels. However, we found that men and women, though having similar physical and functional well-being, reported different QoL determinants, since men seem to rely more on physical adjustment, while women activate more introspective strategies. Positive actions, family issues, negative thoughts, health, and positive thoughts were found to be the most reported themes. In conclusion, the present study strongly suggests that a positive psychological adjustment is possible also in the event of a severe diagnosis and during aggressive treatments, but QoL determinants might be considered too in order to help health professionals to understand patients' experience and to meet their needs.
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Neoplasias Encefálicas/psicología , Cognición/fisiología , Glioma/psicología , Calidad de Vida , Adulto , Neoplasias Encefálicas/epidemiología , Neoplasias Encefálicas/patología , Depresión/epidemiología , Depresión/etiología , Femenino , Glioma/epidemiología , Glioma/patología , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Psicometría , Calidad de Vida/psicología , Encuestas y CuestionariosRESUMEN
Anaplastic gliomas (AG) include 6-10% of all newly diagnoses of primary brain tumors. They have an unfavourable prognosis and, to date, there is not an established treatment universally recognized. Four recent randomized clinical trials were identified for a total of 1,170 patients (anaplastic-astrocytomas, anaplasticoligoastrocytoma, anaplastic-oligodendroglioma), in order to define the better sequence and timing of chemo-radiotherapy, Three studies compared radiotherapy (RT) treatment vs. radio-chemotherapy with procarbazine-lomustine-vincristine (PCV) or temozolomide (TMZ) or dibromodulcitol and bichloroethylnitrosurea (DBD/BCNU) and only one compared RT vs chemotherapy (CT) with PCV or TMZ. Results show no significant differences in terms of PFS/OS between RT/CT alone or combined treatment although a trend toward an improvement of OS was observed after RT + CT treatment (m-OS in RT + adjuvant PCV was 42.3 vs. 30.6 months in RT alone p=0.0003). Grade 3-4 mielotoxicity has been observed in almost all cases of patients treated with PCV + RT. None of four studies reviewed conducted a head to head comparison between PCV vs. TMZ. Only a study randomized patients to PCV/TMZ without however providing data in terms of PSF and OS between the two treatments. It found no significant differences in PFS from initial RT and adjuvant CT (PCV-TMZ) at progression compared to initial CT followed by RT at progression. The optimal treatment of AG should reasonably consider not only the histology as well as the molecular markers of the tumor, but also clinical conditions, age of patients, life expectancy, Karnofsky-performance-status and tumor resection to achieve in future the personalization of care.
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Neoplasias Encefálicas/terapia , Glioma/terapia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Glioma/diagnóstico , Glioma/genética , HumanosRESUMEN
Angiogenesis has recently become a major target for the development of new antineoplastic drugs. The most serious adverse events linked to angiogenesis inhibitors are venous or arterial thromboembolism and haemorrhage. Thus, there is need to define with more certainty the impact of these new drugs in terms of adverse effects in neurological patients. The aim of the study is to assess the risk of venous thromboembolism (VTE) and bleeding in patients with malignant gliomas treated with bevacizumab with or without concomitant anticoagulant therapy. A review of published literature was performed in Medline, from which 476 records were identified. A total of 27 full-text articles, including retrospective analyses, retrospective reviews, and open label trials, were assessed for eligibility. The investigated drugs included bevacizumab alone, bevacizumab plus chemotherapy with/without concomitant radiation therapy; only two articles dealt with bevacizumab in association with anticoagulant treatment. A total of 2,208 patients with malignant gliomas, were identified and included in the analysis. From data it appears that patients receiving bevacizumab had a major risk of developing VTE that increased when bevacizumab is associated with radio-chemotherapy (4.27 vs 7.46 %). Regarding bleeding, data showed that patients treated with anticoagulant had a significantly increased risk of severe central nervous system (CNS) bleeding compared to patients not receiving anticoagulant therapy (0.6 vs 8.2 %). The use of bevacizumab combined with chemo-radiotherapy seems to be associated with a higher risk for VTE compared to patients receiving antiangiogenic therapy alone. The associated use of anticoagulants and bevacizumab far increases the risk of developing CNS and non-CNS bleeding higher than grade 3, compared to patients receiving bevacizumab alone.
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Inhibidores de la Angiogénesis/efectos adversos , Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos/efectos adversos , Neoplasias Encefálicas/tratamiento farmacológico , Glioma/tratamiento farmacológico , Bevacizumab , Humanos , Tromboembolia Venosa/epidemiologíaAsunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Glioma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Compuestos de Nitrosourea/uso terapéutico , Compuestos Organofosforados/uso terapéutico , Terapia Recuperativa , Adulto , Anciano , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Femenino , Estudios de Seguimiento , Glioma/mortalidad , Glioma/patología , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
Neoplastic meningitis (NM) is diagnosed in 1-2 % of patients with primary brain tumors. Standard treatment of NM includes single-agent or combination chemotherapy, with compounds such as methotrexate, thiotepa, and cytarabine (Ara-C) or its injectable, sustained-release formulation Depocyte(®). In this Report, we reported the data of efficacy and tolerability of an intrathecal Depocyte(®) regimen for patients presenting with NM from primary brain tumors. We described 12 patients with NM confirmed at magnetic resonance imaging (MRI) and with a positive cerebrospinal fluid (CSF) cytology. Patients were treated with repeated courses of intrathecal Depocyte(®) (once every 2 weeks for 1 month of induction therapy and as consolidation therapy on a monthly base in responding patients). Twelve patients (10 males and 2 females) were treated by our Institution. The diagnosis of primitive brain tumor was medulloblastoma in six patients, germinoma in two patients, pylocitic astrocytomas with spongioblastic aspects, teratocarcinoma, meningeal melanoma, and ependimoma in the other four patients. The total number of Depocyte(®) cycles ranged from one to nine. In 7/12 patients, there was clinical and/or radiological response after Depocyte(®), and the toxicity was moderate and transient, mainly due to the lumbar puncture procedure. In the two patients with germinoma, we observed a normalization of MRI Imaging and negativization of CSF with disappearance of the tumor cells. OS was 180 days (range 20-300, CI 95 %).
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Antimetabolitos Antineoplásicos/administración & dosificación , Neoplasias Encefálicas/patología , Citarabina/administración & dosificación , Neoplasias Meníngeas/tratamiento farmacológico , Neoplasias Meníngeas/secundario , Meningitis/tratamiento farmacológico , Adulto , Antimetabolitos Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/complicaciones , Citarabina/uso terapéutico , Femenino , Humanos , Liposomas , Masculino , Neoplasias Meníngeas/líquido cefalorraquídeo , Neoplasias Meníngeas/patología , Meningitis/líquido cefalorraquídeo , Meningitis/etiología , Meningitis/patología , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
Neoplastic dissemination to the leptomeninges is an increasingly common occurrence in patients with both haematological and solid tumors arising outside the central nervous system. Both refinement of diagnostic techniques (Magnetic resonance imaging) and increased survival in patients treated with targeted therapies for systemic tumors account for this increased frequency. Cerebrospinal fluid cytological analysis and MRI confirm clinical diagnosis based on multifocal central nervous system signs/symptoms in a patient with known malignancy. Overall survival in patients with leptomeningeal neoplastic dissemination from solid tumors is short, rarely exceeding 3-4 months. However, selected patients may benefit from aggressive therapies, Apart from symptomatic treatment, intrathecal chemotherapy is used, with both free (methotrexate, Thiotepa, AraC) and liposomal antitumor agents (liposomal AraC). Palliative radiotherapy is indicated only in cases of symptomatic bulky disease, surgery is limited to positioning of Ommaya recervoirs or C5F shunting. We report clinical data on a cohort of 26 prospectively followed patients with neoplastic leptomeningitis followed in Lombardia, Italy, in 2011. Prognostic factors and pattern of care are reported.
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Partial seizures can be due to a growing cerebral lesion, which may be tumoral or inflammatory/infectious in nature. The differential diagnosis is obviously important; increasing immigration to Europe from Africa is leading to an increase of infectious disease involving also the central nervous system. The authors report imaging the a case of a brain tuberculoma due to Mycobacterium africanum mimicking brain tumor, in which diagnosis was possible by inoculum in guinea-pig of material obtained by mediastinal biopsy of enlarged lymph nodes. Specific treatment led to marked reduction in the size of the brain lesion.
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Infecciones por Mycobacterium/complicaciones , Tuberculoma Intracraneal/diagnóstico , Tuberculoma Intracraneal/etiología , Adulto , Antituberculosos/uso terapéutico , Humanos , Imagen por Resonancia Magnética , Masculino , Infecciones por Mycobacterium/tratamiento farmacológico , Radiografía Torácica , Tuberculoma Intracraneal/tratamiento farmacológicoRESUMEN
In 1991, a prospective phase II trial was initiated to evaluate the efficacy of treatment for adults with medulloblastoma (MB). After surgery, patients were staged with a neuroradiologic examination of the brain and neuroaxis and by cerebrospinal fluid cytology. All patients received three cycles of upfront cisplatinum (cisplatinum) and etoposide (VP16) chemotherapy followed by cranio-spinal radiation therapy. The current article reports on the long-term results from that trial. After a median follow-up of 14.9 years, among a total of 28 adults with MB, the overall progression-free survival and overall survival (OS) rates at 5 years were 57.6 and 80%, respectively. The median OS for the whole group of patients was 11.3 years. The observed toxicity was mainly hematological, with leukopenia and thrombocytopenia (16% of grades 3 and 4). In summary, in our small series of patients, the role of combination administration of CDDP + VP16 started before the initiation of radiotherapy in reducing recurrences, particularly distant recurrences, remains unclear. To know whether adding chemotherapy to craniospinal radiation in adult therapy increases relapse-free and overall survival, we must await the results of a larger randomized controlled clinical trial.
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Antineoplásicos/administración & dosificación , Neoplasias Cerebelosas/tratamiento farmacológico , Cisplatino/administración & dosificación , Etopósido/administración & dosificación , Meduloblastoma/tratamiento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Cerebelosas/mortalidad , Neoplasias Cerebelosas/radioterapia , Femenino , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Meduloblastoma/mortalidad , Meduloblastoma/radioterapia , Persona de Mediana Edad , Análisis de SupervivenciaRESUMEN
Despite a confirmed survival benefit associated with adjuvant radio- and chemotherapy, the majority of patients with malignant glioma relapse after initial therapy. Recurrent malignant glioma treatment has not been standardised and usually the response rate to standard chemotherapy protocols for recurrent malignant glioma is less than 30%. The growing body of evidence demonstrating the clinical importance of O6-methylguanine methyltransferase (MGMT) has generated a considerable interest in the exploration of strategies to overcome MGMT-mediated resistance to alkylating agents; for example protracted administration of Temozolomide (TMZ) may result in more extensive and sustained depletion of MGMT; for this reason a variety of dosing schedules that increase the duration of exposure and the cumulative dose of TMZ are being investigated for the treatment of patient with recurrent malignant glioma after standard treatment. The most widely studied regimens in this setting include (1) 21 of 28-day schedule at a dose of 75-100 mg/m(2)/day; (2) 7 of 14-day schedule at a dose of 150 mg/m(2)/day, also referred to as the ''one week on/one week off'' schedule; (3) Continuous daily schedule at a dose of 50 mg/m(2)/day. An alternative dosing schedule of TMZ may be a reasonable option in patients having high-grade gliomas with recurrence after standard therapy.
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Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Dacarbazina/análogos & derivados , Glioma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Encefálicas/patología , Dacarbazina/uso terapéutico , Esquema de Medicación , Glioma/patología , Humanos , Retratamiento , TemozolomidaRESUMEN
Fotemustine (FTMS) is a third-generation nitrosourea, in preclinical studies, FTMS compared favorably with carmustine (BCNU) and lomustine (CCNU) against several human tumor cell lines. In conventional schedule, FTMS is administered at a dose of 100 mg/sqm/week for three consecutive weeks as induction (I) treatment, followed by 100 mg/sqm every three weeks, after a 5-week rest, as maintenance (M). Several Italian groups reported the results using FTMS in malignant glioma patients recurring after temozolomide standard treatment. In these papers, the 6-progression free survival are ranging from 20 to 52%. With the schedule (I + M) myelosuppression is observed in more than 30% of patients, and thrombocytopenia and leukopenia are more frequent and significant in Temozolomide pretreated patients. On the bases of the hematological toxicities several authors experimented new schedules of FTMS administrated at low doses. Recently, some authors reported the interesting results of a multicenter study on recurrent glioblastoma multiforme patients combining FTMS with new antiangiogentic agent bevacizumab.
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Antineoplásicos Alquilantes/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Compuestos de Nitrosourea/uso terapéutico , Compuestos Organofosforados/uso terapéutico , Neoplasias Encefálicas/patología , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Glioblastoma/patología , HumanosRESUMEN
Infections represent a serious and frequent complication in neuro-oncology patients. Decreased immune defences, along with poor nutritional status are the main predisposition factors. The combined therapeutic strategies of chemotherapy and radiotherapy may favour bone marrow depression and further increase the risk of developing opportunistic infections in brain tumour patients. The spectrum of infections in neuro-oncology patients is large and includes opportunistic infections by bacteria, viruses, fungi and parasites. Importantly, a high index of suspicion for opportunistic infections in general should be maintained, especially in glioma patients receiving dose-dense schedules of temozolomide. After neurosurgical procedures, infections most commonly present as meningitis, subdural empyema, or cerebral abscess. Infections represent a frequent and possibly serious complication in general immunocompromised oncology population. It should be underlined that infections are not limited to immunocompromised patients, being also present at the early disease stages, especially due to therapeutic strategies (chemo and radiotherapy, surgical procedures). Therefore this issue deserves more attention in neuroncology setting.
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Neoplasias Encefálicas/inmunología , Glioma/inmunología , Huésped Inmunocomprometido/inmunología , Infecciones Oportunistas/inmunología , Neoplasias Encefálicas/complicaciones , Glioma/complicaciones , Humanos , Infecciones Oportunistas/clasificación , Infecciones Oportunistas/complicacionesRESUMEN
The impossibility to conduct a histological diagnosis could be due to different reasons: (1) patient's refusal to undergo surgery/biopsy. (2) Technical difficulties: despite the advance in surgical procedures, the removal of lesions that are located either in critical or in deep areas represents a considerable risk for patients. (3) Quality/quantity of the sample. In rare cases even when the surgical sample is achieved it could be impossible to reach a histological confirmation, for example due to the small amount of tissue obtained. The lack of histology leads to suboptimal therapy, incorrect prognosis, and misinterpretation of clinical trials and furthermore undermines the possibility to perform most radiation and chemotherapy protocols. In this setting the morphological data obtained with conventional MR imaging may be integrated with the metabolic, structural and perfusional information provided by new MR and metabolic techniques (spectroscopy, SPECT, PET in particular).
Asunto(s)
Biopsia/métodos , Neoplasias Encefálicas/patología , Encéfalo/patología , Neuroimagen/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/cirugía , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía , Técnicas Histológicas , Humanos , Clasificación del Tumor/métodos , Neuroimagen/instrumentación , Procedimientos Neuroquirúrgicos , Aceptación de la Atención de Salud , Radiografía , CintigrafíaRESUMEN
Brain tumor symptoms vary greatly from person to person because of two factors: location and size of tumors. The size of a tumor, however, does not necessarily affect the severity of symptoms. Manifestations depend on the cause of the symptoms: an increase in ICP, direct compression of gray or white matter, shifting of intracranial contents, or secondary cerebral ischemia. Symptoms may be non-specific and include headache, altered mental status, ataxia, nausea, vomiting, weakness, and gait disturbance. Left-sided weakness may be seen in a patient with a tumor pressing on the contra-lateral motor strip or speech difficulties may occur if a tumor is in the dominant hemisphere. Up to a third of people report having seizures prior to being diagnosed with a brain tumor. Rarely, brain tumor can present with psychiatric symptoms but without other neurological signs or symptoms. Evaluation for brain tumor is indicated in any patient with chronic, persistent headache associated with protracted nausea, vomiting, seizures, changes in headache pattern, neurologic symptoms, and change in personality.
Asunto(s)
Neoplasias Encefálicas/diagnóstico , Epilepsia/complicaciones , Glioma/diagnóstico , Trastornos Mentales/etiología , Convulsiones/etiología , Factores de Edad , Anciano , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/fisiopatología , Niño , Diagnóstico Precoz , Epilepsia/patología , Epilepsia/fisiopatología , Lateralidad Funcional , Glioma/complicaciones , Glioma/fisiopatología , Humanos , Trastornos Mentales/patología , Trastornos Mentales/fisiopatología , Persona de Mediana Edad , Convulsiones/patologíaRESUMEN
In malignant gliomas, the management of symptoms and minimization of side effects assume major importance. Corticosteroids provide transient relief from neurological symptoms. However, treatment with steroids is also commonly associated with considerable side-effects including: hyperglycemia, osteoporosis, myopathy, lymphopenia and others. Sometimes, antiepileptic drugs may contribute to clinical decline of neuro-oncological patients in stable disease not only by neuropsychological impairment but also by metabolic interations. Several studies have demonstrated a high frequency of hyponatremia among patients treated with carbamazepine and particularly with oxacarbamazepine. Venous thromboembolism is a common complication in patients with cancer and it is particularly high in malignant gliomas, occurring in approximately 20-30% of such patients. Prophylactic treatment in patients with glioblastoma is a key topic. The role of prophylaxis has not yet been established with certainty. Overall the data show a clear reduction of venous thromboembolic events in patients treated with intermittent pneumatic compression (IPC). The addition of enoxaparin dose of 6.000 UI, starting in the perioperative period, induces an increase of major bleeding events. In the absence of availability of IPC, the use of enoxaparin 4.000 UI in addition to graduated compression stockings, reduces thromboembolic events without major bleeding events.