RESUMEN
Gliosarcoma is a rare histopathological subtype of glioblastoma. Metastatic spreading is unusual. In this report, we illustrate a case of gliosarcoma with extensive extracranial metastases with confirmation of histological and molecular concordance between the primary tumor and a metastatic lesion of the lung. Only the autopsy revealed the extent of metastatic spread and the hematogenous pattern of metastatic dissemination. Moreover, the case bared a familial coincidence of malignant glial tumors as the patient's son was diagnosed with a high-grade glioma shortly after the patient's death. By molecular analysis (Sanger and next generation panel sequencing), we could confirm that both patient's tumors carried mutations in the TP53 gene. Interestingly, the detected mutations were located in different exons. Altogether, this case draws attention to the fact that sudden clinical aggravation could be caused by the rare phenomenon of metastatic spread and should therefore be always taken into consideration, even at an early disease stage. Furthermore, the presented case highlights the contemporary value of autoptic pathological examination.
Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Gliosarcoma , Neoplasias Pulmonares , Humanos , Gliosarcoma/genética , Gliosarcoma/diagnóstico , Gliosarcoma/patología , Neoplasias Encefálicas/patología , Glioblastoma/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundario , Pulmón/patologíaRESUMEN
PURPOSE: In the randomized phase III trial CeTeG/NOA-09, temozolomide (TMZ)/lomustine (CCNU) combination therapy was superior to TMZ in newly diagnosed MGMT methylated glioblastoma, albeit reporting more frequent hematotoxicity. Here, we analyze high grade hematotoxicity and its prognostic relevance in the trial population. METHODS: Descriptive and comparative analysis of hematotoxicity adverse events ≥ grade 3 (HAE) according to the Common Terminology of Clinical Adverse Events, version 4.0 was performed. The association of HAE with survival was assessed in a landmark analysis. Logistic regression analysis was performed to predict HAE during the concomitant phase of chemotherapy. RESULTS: HAE occurred in 36.4% and 28.6% of patients under CCNU/TMZ and TMZ treatment, respectively. The median onset of the first HAE was during concomitant chemotherapy (i.e. first CCNU/TMZ course or daily TMZ therapy), and 42.9% of patients with HAE receiving further courses experienced repeat HAE. Median HAE duration was similar between treatment arms (CCNU/TMZ 11.5; TMZ 13 days). Chemotherapy was more often discontinued due to HAE in CCNU/TMZ than in TMZ (19.7 vs. 6.3%, p = 0.036). The occurrence of HAE was not associated with survival differences (p = 0.76). Regression analysis confirmed older age (OR 1.08) and female sex (OR 2.47), but not treatment arm, as predictors of HAE. CONCLUSION: Older age and female sex are associated with higher incidence of HAE. Although occurrence of HAE was not associated with shorter survival, reliable prediction of patients at risk might be beneficial to allow optimal management of therapy and allocation of supportive measures. TRIAL REGISTRATION: NCT01149109.
Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Humanos , Femenino , Temozolomida/uso terapéutico , Lomustina/uso terapéutico , Pronóstico , Dacarbazina/efectos adversos , Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Antineoplásicos Alquilantes/efectos adversosRESUMEN
BACKGROUND: Diffuse lower WHO grade II and III gliomas (LGG) are slowly progressing brain tumors, many of which eventually transform into a more aggressive type. LGG is characterized by widespread genetic and transcriptional heterogeneity, yet little is known about the heterogeneity of the DNA methylome, its function in tumor biology, coupling with the transcriptome and tumor microenvironment and its possible impact for tumor development. METHODS: We here present novel DNA methylation data of an LGG-cohort collected in the German Glioma Network containing about 85% isocitrate dehydrogenase (IDH) mutated tumors and performed a combined bioinformatics analysis using patient-matched genome and transcriptome data. RESULTS: Stratification of LGG based on gene expression and DNA-methylation provided four consensus subtypes. We characterized them in terms of genetic alterations, functional context, cellular composition, tumor microenvironment and their possible impact for treatment resistance and prognosis. Glioma with astrocytoma-resembling phenotypes constitute the largest fraction of nearly 60%. They revealed largest diversity and were divided into four expression and three methylation groups which only partly match each other thus reflecting largely decoupled expression and methylation patterns. We identified a novel G-protein coupled receptor and a cancer-related 'keratinization' methylation signature in in addition to the glioma-CpG island methylator phenotype (G-CIMP) signature. These different signatures overlap and combine in various ways giving rise to diverse methylation and expression patterns that shape the glioma phenotypes. The decrease of global methylation in astrocytoma-like LGG associates with higher WHO grade, age at diagnosis and inferior prognosis. We found analogies between astrocytoma-like LGG with grade IV IDH-wild type tumors regarding possible worsening of treatment resistance along a proneural-to-mesenchymal axis. Using gene signature-based inference we elucidated the impact of cellular composition of the tumors including immune cell bystanders such as macrophages. CONCLUSIONS: Genomic, epigenomic and transcriptomic factors act in concert but partly also in a decoupled fashion what underpins the need for integrative, multidimensional stratification of LGG by combining these data on gene and cellular levels to delineate mechanisms of gene (de-)regulation and to enable better patient stratification and individualization of treatment.
Asunto(s)
Neoplasias Encefálicas/genética , Metilación de ADN/genética , Dosificación de Gen , Glioma/genética , Transcriptoma , Neoplasias Encefálicas/complicaciones , Biología Computacional , Epigénesis Genética , Humanos , Clasificación del Tumor , Microambiente Tumoral/genética , Organización Mundial de la SaludRESUMEN
BACKGROUND: Cancer research has made great progress in the recent years. With the increasing number of options in diagnosis and therapy the implementation of tumorboards (TUBs) has become standard procedure in the treatment of cancer patients. Adherence tests on tumor board decisions are intended to enable quality assurance and enhancement for work in tumor boards in order to continuously optimize treatment options for cancer patients. METHODS: Subject of this study was the adherence of the recommendations made in three of 14 tumorboards, which take place weekly in the Center for Integrated Oncology (CIO) at the University Hospital Bonn. In total, therapy recommendations of 3815 patient cases were checked on their implementation. A classification into four groups has been made according to the degree of implementation. A second classification followed regarding the reasons for differences between the recommendation and the therapy which the patient actually received. RESULTS: The study showed that 80.1% of all recommendations in the three TUBs were implemented. 8.3% of all recommendations showed a deviance. Most important reasons for the deviances were patient wish (36.5%), patient death (26%) and doctoral decision, due to the patient's comorbidities or side effects of the treatment (24.1%).Interestingly, deviance in all three tumor boards in total significantly decreased over time. CONCLUSIONS: Aim of the study was to clarify the use of tumor boards and find approaches to make them more efficient. Based on the results efficiency might be optimized by increased consideration of patients` preferences, improved presentation of patient-related data, more detailed documentation and further structuring of the tumor board meetings.
Asunto(s)
Adhesión a Directriz , Oncología Integrativa , Investigación Interdisciplinaria/organización & administración , Neoplasias/terapia , Alemania , HumanosRESUMEN
Leptomeningeal metastasis (LM), i.e. the seeding of tumor cells to the cerebrospinal fluid (CSF) and the leptomeninges, is a devastating and mostly late-stage complication of various solid tumors. Clinical signs and symptoms may include cranial nerve palsies, radicular symptoms, signs of increased intracranial pressure such as headache, nausea and vomiting, and cognitive dysfunction. In cases of suspected LM, the highest diagnostic sensitivity is provided by the combination of CSF cytology and contrast-enhanced MRI (cranial as well as complete spine). The therapeutic spectrum includes radiotherapy of the clinically involved region as well as systemic and intrathecal chemotherapy. The choice of treatment modalities depends on the type of LM (non-adherent tumor cells in the CSF vs. nodular contrast-enhancing tumor growth), additional systemic involvement (uncontrolled vs. controlled systemic disease) and additional involvement of the CNS parenchyma (LM as the only CNS involvement vs. LM+parenchymal CNS metastases). Larger contrast-enhancing nodular LM or symptomatic lesions of the spine may be treated with radiotherapy. In case of uncontrolled systemic disease, the treatment regimen should include systemic chemotherapy. The choice of systemic treatment should take into account the histology of the primary tumor. Intrathecal chemotherapy is most important in cases of LM of the non-adherent type. There are three substances for routine use for intrathecal chemotherapy: methotrexate, cytarabine, and thiotepa. Liposomal cytarabine shows advantages in terms of longer injection intervals, a sufficient distribution in the entire subarachnoid space after lumbar administration and improved quality-of-life. The role of new agents (e.g. rituximab and trastuzumab) for intrathecal therapy is still unclear.
Asunto(s)
Antineoplásicos/uso terapéutico , Citarabina/uso terapéutico , Neoplasias Meníngeas , Metotrexato/uso terapéutico , Humanos , Inyecciones Espinales , Neoplasias Meníngeas/líquido cefalorraquídeo , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/fisiopatología , Neoplasias Meníngeas/secundario , Neoplasias Meníngeas/terapia , Siembra Neoplásica , Estadificación de Neoplasias , Radioterapia/métodos , Tiotepa/uso terapéutico , Resultado del TratamientoRESUMEN
Therapeutic concepts for malignant gliomas increasingly target the genetically non-transformed tumor stroma rather than the tumor cells themselves. There are two particular compartments of the tumor stroma which are currently tackled: the vascular compartment by using antiangiogenic treatment with the aim of vascular normalization and the immune compartment with the aim of enhancing or inducing anti-tumor immunity. Although the vascular endothelial growth factor (VEGF) A antibody bevacizumab has not been approved for the treatment of malignant glioma in European countries, there is evidence from smaller trials of biological efficacy particularly in recurrent disease and the results of a large European phase III study testing the clinical efficacy are currently expected. Immunotherapies are on the verge of entering the clinical arena with the first randomized phase III clinical trials having already been completed. In these studies, active vaccination and checkpoint inhibitors which are approved for other tumor entities are being tested. This article provides an overview on the current antiangiogenic and immunological therapies for gliomas, summarizes the results of clinical trials and discusses further developments.
Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Neoplasias Encefálicas/terapia , Vacunas contra el Cáncer/uso terapéutico , Glioma/terapia , Inmunosupresores/uso terapéutico , Neovascularización Patológica/terapia , Animales , Neoplasias Encefálicas/inmunología , Glioma/inmunología , Humanos , Inmunoterapia/métodos , Neovascularización Patológica/inmunología , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunologíaRESUMEN
BACKGROUND AND PURPOSE: Recently two retrospective cohort studies report efficacy of bevacizumab in patients with recurrent atypical and anaplastic meningioma. Another successful therapeutic option of bevacizumab seems to be treatment of cerebral radiation necrosis. However, the antiangiogenic effects in MRI diffusion and perfusion in meningiomas have not been previously described in detail. The objective of this research was to evaluate the clinical and MR imaging effects of bevacizumab in a malignant meningioma patient harboring additional cerebral radiation necrosis. CASE PRESENTATION: We report the case of an 80-year-old woman who underwent bevacizumab therapy (5 mg/kg every 2 weeks for 2 months) for treatment of a symptomatic radiation necrosis in malignant meningiomatosis of World Health Organization (WHO) grade III. The patient was closely monitored with MRI including diffusion and perfusion studies. Upon bevacizumab therapy, the clinical situation was well stabilized over a period of 4 months until the patient unfortunately died due to pneumonia/septicemia probably unrelated to bevacizumab therapy. Consecutive MRI demonstrated 4 important aspects: (1) considerable decrease of the contrast medium (CM)-enhanced radiation necrosis, (2) mixed response with respect to the meningiomatosis with stable and predominantly growing tumor lesions, (3) a new diffusion-weighted imaging (DWI) lesion in a CM-enhanced tumor as described in gliomas, which we did not interpret as a response to bevacizumab therapy, and (4) new thrombembolic infarcts, which are a known side-effect of bevacizumab treatment. CONCLUSION: Bevacizumab is effective in the treatment of radiation necrosis. We could not confirm the potential antitumor effect of bevacizumab in this patient. However, we could describe several new radiographic effects of bevacizumab therapy in malignant meningioma.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Lesiones Encefálicas/tratamiento farmacológico , Neoplasias Meníngeas/terapia , Meningioma/terapia , Traumatismos por Radiación/tratamiento farmacológico , Radioterapia Conformacional/efectos adversos , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/uso terapéutico , Bevacizumab , Lesiones Encefálicas/patología , Imagen de Difusión por Resonancia Magnética/métodos , Femenino , Humanos , Angiografía por Resonancia Magnética/métodos , Neoplasias Meníngeas/patología , Meningioma/patología , Traumatismos por Radiación/patología , Resultado del TratamientoRESUMEN
We report a now 74-year-old patient who was successfully treated with a methotrexate (MTX)-ssbased polychemotherapy protocol (Bonn protocol) for primary central nervous system lymphoma (PCNSL) in 1996. When presenting with an unusually late relapse after 13 years of tumor-free survival the diagnosis was made on the basis of clinical and radiological criteria. In the context of the very limited treatment options for recurrent PCNSL, it is reassuring that the re-application of high dose-MTX-based polychemotherapy, including intraventricular treatment, again succeeded in a sustained complete response with still low neurotoxicity.
Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Metotrexato/uso terapéutico , Anciano , Neoplasias del Sistema Nervioso Central/patología , Humanos , Linfoma de Células B Grandes Difuso/patología , Persona de Mediana Edad , Recurrencia , Inducción de RemisiónRESUMEN
After failure of temozolomide, there is no established standard salvage chemotherapy for patients with recurrent glioblastoma (GBM). Two phase II trials combining ifosfamide, carboplatin and etoposide chemotherapy (ICE) showed favorable results. We therefore applied the ICE protocol to 13 patients (10 GBM, 3 anaplastic astrocytomas). Partial or complete remissions were not observed. None of the 13 patients survived progression-free for 6 months. Our retrospective analysis suggests that the ICE regimen is not effective in patients with recurrent high-grade glioma if applied at second or third relapse.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Astrocitoma/tratamiento farmacológico , Neoplasias Encefálicas/tratamiento farmacológico , Glioma/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Astrocitoma/secundario , Neoplasias Encefálicas/patología , Carboplatino/administración & dosificación , Dacarbazina/análogos & derivados , Dacarbazina/uso terapéutico , Esquema de Medicación , Etopósido/administración & dosificación , Femenino , Glioma/secundario , Humanos , Ifosfamida/administración & dosificación , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Temozolomida , Insuficiencia del TratamientoAsunto(s)
Anticuerpos Monoclonales/uso terapéutico , Neoplasias Meníngeas/tratamiento farmacológico , Meningioma/tratamiento farmacológico , Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales Humanizados , Antineoplásicos/uso terapéutico , Bevacizumab , Femenino , Humanos , Persona de Mediana Edad , Inducción de Remisión/métodos , Resultado del TratamientoRESUMEN
Neurological complications of therapeutic procedures for brain tumors are increasingly being recognized. These encompass the classic types of central and peripheral neurotoxicity, such as radiotherapy-induced leukoencephalopathy and platinum-induced neuropathy. However, the advent of novel protocols and targeted therapeutics has expanded the spectrum of neurological complications. A problem of considerable importance is pseudoprogression after radiochemotherapy with temozolomide. Among the new targeted drugs complications of therapy with bevacizumab are the subject of intense discussion. In this review article the neurotoxic potential of intrathecal chemotherapy, kinase inhibitors, immunological strategies and local therapies are summarized. Knowledge about neurological complications of brain tumor therapy procedures is important for risk assessment and patient information.
Asunto(s)
Antineoplásicos/efectos adversos , Antineoplásicos/toxicidad , Daño Encefálico Crónico/inducido químicamente , Daño Encefálico Crónico/diagnóstico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/radioterapia , Encéfalo/efectos de los fármacos , Encéfalo/efectos de la radiación , Irradiación Craneana/efectos adversos , Traumatismos por Radiación/diagnóstico , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/toxicidad , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/toxicidad , Anticuerpos Monoclonales Humanizados , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/toxicidad , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Bevacizumab , Neoplasias Encefálicas/mortalidad , Terapia Combinada , Supervivencia sin Enfermedad , Humanos , Inyecciones Espinales , Leucoencefalopatías/diagnóstico , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/toxicidad , Nervios Periféricos/efectos de los fármacos , Nervios Periféricos/efectos de la radiación , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/toxicidadRESUMEN
Seizures complicate the clinical course of > 80% of patients with low-grade gliomas. Patients with some tumor variants almost always have epilepsy. Diffuse low-grade gliomas (LGG) are believed to cause epilepsy through partial deafferentiation of nearby brain cortex (denervation hypersensitivity). Glioneural tumors may interfere with local neurotransmitter levels and are sometimes associated with structural abnormalities of the brain which may produce seizures. The severity of tumor associated epilepsy varies considerably between patients. Some cases may present with a first seizure. Others suffer from long-standing pharmacoresistant epilepsy. Seizure control rates of > 70-80% can be expected after complete tumor resections. Patients with drug-resistant epilepsy require a comprehensive preoperative epileptological work-up which may include the placement of subdural (and intraparenchymal) electrodes or intraoperative electrocorticography (ECoG) for the delineation of extratumoral seizure foci. Partial and subtotal tumor resections are helpful in selected cases, i.e. for gliomas involving the insula. In one series, 40% of patients presented for surgery with uncontrolled seizures, i.e. medical therapy alone often fails to control tumor-related epilepsy. Use of the newer (second generation) non-enzyme inducing antiepileptic drugs (non-EIAED) is encouraged since they seem to have lesser interactions with other medications (e.g. chemotherapy). Chemotherapy and irradiation may have some minor beneficial effects on the patients' seizure disorder. Overall 60-70% of patients may experience recurrent epilepsy during long-term follow-up. Recurrent seizures (not infrequently heralding tumor recurrence) after surgery continue to pose significant clinical problems.
Asunto(s)
Neoplasias Encefálicas/patología , Glioma/patología , Convulsiones/epidemiología , Convulsiones/terapia , Anticonvulsivantes/uso terapéutico , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/terapia , Glioma/complicaciones , Glioma/terapia , Humanos , Incidencia , Convulsiones/diagnósticoRESUMEN
BACKGROUND: In a previous trial (NOA-01), the combination of nimustine and teniposide showed efficacy in previously untreated glioblastoma (GBM). After establishing temozolomide as standard first-line therapy in GBM patients, the nimustine (ACNU)/teniposide (VM-26) combination has been employed as salvage chemotherapy for recurrent GBM. However, data on the toxicity and efficacy of this regimen in recurrent GBM are lacking. PATIENTS AND METHODS: In two neurooncological centers, all patients with recurrent GBM treated with nimustine (90 mg/m(2), day 1/42) and teniposide (45-70 mg/m(2), days 1-3/42) were analyzed retrospectively for progression-free survival (PFS), overall survival (OS) and toxicity. RESULTS: Thirty-five patients (median age 51 years, range 25-71 years) were identified. Six months after chemotherapy initiation, PFS was 29% and the median OS 6 months; 23% of patients were alive > or = 1 year after initiation of nimustine-teniposide chemotherapy. Grade 4 hematotoxicity was observed in 12 of 35 patients (34%) and in 14 of 83 evaluable chemotherapy courses (17%). CONCLUSIONS: The benefit of the nimustine-teniposide combination is moderate in patients with recurrent GBM. The data support the efficacy of the nimustine-teniposide chemotherapy, but the rate of high-grade hematotoxicity is increased.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Nimustina/administración & dosificación , Tenipósido/administración & dosificación , Adulto , Anciano , Neoplasias Encefálicas/mortalidad , Femenino , Glioblastoma/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Nimustina/efectos adversos , Estudios Retrospectivos , Tenipósido/efectos adversosRESUMEN
OBJECTIVE: To describe the demographics, diagnostic details, therapeutic management, and outcome in patients with primary CNS lymphoma (PCNSL) with ocular involvement. METHODS: A retrospective study of 221 patients was assembled from 16 centers in seven countries. Only HIV-negative, immunocompetent patients with brain and ocular lymphoma were included; none had systemic lymphoma. RESULTS: Median age at diagnosis was 60. Fifty-seven percent were women. Median Eastern Cooperative Oncology Group performance status was 2. Ocular disturbance and behavioral/cognitive changes were the most common presenting symptoms. Diagnosis of lymphoma was made by brain biopsy (147), vitrectomy (65), or CSF cytology (11). Diagnosis of intraocular lymphoma was made by vitrectomy/choroidal/retinal biopsy (90) or clinical ophthalmic examination (141). CSF cytology was positive in 23%. Treatment information was available for 176 patients. A total of 102 received dedicated ocular therapy (ocular radiotherapy 79, intravitreal methotrexate 22, and both 1) in addition to treatment for their brain lymphoma. Sixty-nine percent progressed at a median of 13 months; sites of progression included brain 52%, eyes 19%, brain and eyes 12%, and systemic 2%. Patients treated with local ocular therapy did not have a statistically significant decreased risk of failing in the eyes (p = 0.7). Median progression free survival and overall survival for the entire cohort were 18 and 31 months. CONCLUSION: This is the largest reported series of primary CNS lymphoma (PCNSL) with intraocular involvement. Progression free and overall survival was similar to that reported with PCNSL. Dedicated ocular therapy improved disease control but did not affect overall survival.
Asunto(s)
Neoplasias del Sistema Nervioso Central/epidemiología , Conducta Cooperativa , Neoplasias del Ojo/epidemiología , Linfoma/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Sistema Nervioso Central/complicaciones , Neoplasias del Sistema Nervioso Central/terapia , Neoplasias del Ojo/complicaciones , Neoplasias del Ojo/terapia , Femenino , Estudios de Seguimiento , Humanos , Internacionalidad , Linfoma/complicaciones , Linfoma/terapia , Masculino , Persona de Mediana Edad , Investigación/tendencias , Estudios Retrospectivos , Tasa de Supervivencia/tendenciasAsunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Neoplasias de la Mama/patología , Carcinoma/terapia , Citarabina/administración & dosificación , Neoplasias Meníngeas/terapia , Encéfalo/patología , Carcinoma/tratamiento farmacológico , Carcinoma/radioterapia , Carcinoma/secundario , Femenino , Humanos , Liposomas , Neoplasias Meníngeas/tratamiento farmacológico , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/secundario , Persona de Mediana Edad , Radioterapia AdyuvanteRESUMEN
BACKGROUND: Primary intraocular lymphoma (PIOL) is an uncommon subset of primary central nervous system lymphoma. Because it is rare and difficult to diagnose, the natural history and optimal management are unknown. PATIENTS AND METHODS: A retrospective study of 83 HIV negative, immunocompetent PIOL patients was assembled from 16 centers in seven countries. RESULTS: Median age at diagnosis was 65. Median ECOG performance status was 0. Presenting symptoms included blurred vision, decreased visual acuity, and floaters. Median time to diagnosis was 6 months. Diagnosis was made by vitrectomy (74), choroidal/retinal biopsy (6) and ophthalmic exam (3). Eleven percent had positive CSF cytology. Initial treatment was categorized as focal in 23 (intra-ocular methotrexate, ocular radiotherapy) or extensive in 53 (systemic chemotherapy, whole brain radiotherapy). Six received none; details are unknown in one. Forty-seven relapsed: brain 47%, eyes 30%, brain and eyes 15%, and systemic 8%. Median time to relapse was 19 months. Focal therapy alone did not increase risk of brain relapse. Median progression free (PFS) and overall survival (OS) were 29.6 and 58 months, respectively, and unaffected by treatment type. CONCLUSION: Treatment type did not affect relapse pattern, median PFS or OS. Focal therapy may minimize treatment toxicity without compromising disease control.
Asunto(s)
Neoplasias del Ojo/mortalidad , Neoplasias del Ojo/patología , Linfoma no Hodgkin/mortalidad , Linfoma no Hodgkin/patología , Recurrencia Local de Neoplasia/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias del Sistema Nervioso Central/mortalidad , Neoplasias del Sistema Nervioso Central/patología , Neoplasias del Sistema Nervioso Central/terapia , Terapia Combinada , Consenso , Neoplasias del Ojo/terapia , Femenino , Seronegatividad para VIH , Humanos , Linfoma no Hodgkin/terapia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , Radioterapia Adyuvante , Estudios Retrospectivos , Medición de Riesgo , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Progressive multifocal leukoencephalopathy (PML) is caused by the replication of JC virus in oligodendrocytes of immunocompromised patients. Diagnosis usually relies on the polymerase chain reaction (PCR)-based demonstration of JC virus DNA in the cerebrospinal fluid. As previous reports have suggested that some patients may benefit from antiviral therapy, non-invasive early diagnosis is highly desirable. Repetitive magnetic resonance imaging (MRI) examinations (two to nine) were obtained in seven patients (aged 40-67 years, six males, one female) with classical clinical and imaging findings of PML. Five patients had underlying hematological disorders and two acquired immune deficiency syndrome. PCR of the cerebrospinal fluid (CSF) specimen was positive for JC virus DNA in six patients. MRI sequences included T2-, T1- and diffusion-weighted (DW) images in all patients and diffusion-tensor imaging (DTI) in four cases. DTI was once performed at 3T, in the remaining patients at 1.5T. All patients received antiviral treatment with cidofovir in addition to the treatment of the underlying disorder. MRI showed areas of T2 hyperintensity with involvement of the subcortical U-fibers and restricted diffusion in all patients. Areas of diffusion abnormality correlated with disease progress. Contrast enhancement was encountered once after successful treatment and heralded clinical remission with virus elimination from the CSF. Hence, MRI including DW and contrast-enhanced images may be used to evaluate disease activity. Contrast enhancement may indicate an inflammatory response and thus herald immunologic virus elimination.
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Medios de Contraste , Imagen de Difusión por Resonancia Magnética/métodos , Leucoencefalopatía Multifocal Progresiva/patología , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Encéfalo/patología , Femenino , Humanos , Leucoencefalopatía Multifocal Progresiva/líquido cefalorraquídeo , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Pesos y MedidasAsunto(s)
Anticuerpos Monoclonales/administración & dosificación , Neoplasias Encefálicas/tratamiento farmacológico , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Anticuerpos Monoclonales de Origen Murino , Neoplasias Encefálicas/cirugía , Infecciones por Virus de Epstein-Barr/cirugía , Humanos , Infusiones Intravenosas , Linfoma no Hodgkin/cirugía , Rituximab , Trasplante de Células Madre , Trasplante HomólogoRESUMEN
The authors administered procarbazine, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU, lomustine), and vincristine (PCV) to 86 patients with recurrent glioblastoma. There were three partial responses, but no complete responses. Median progression-free survival was 17.1 weeks and progression-free survival at 6 months was 38.4%. World Health Organization grade III/IV hematologic toxicity was common (25.6%), but nonhematologic toxicity was mild.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Lomustina/administración & dosificación , Masculino , Persona de Mediana Edad , Procarbazina/administración & dosificación , Recurrencia , Factores de Tiempo , Vincristina/administración & dosificaciónRESUMEN
The authors performed a comprehensive analysis of the functional outcome of 10 patients who had survived 5 years from a diagnosis of glioblastoma. Neurologic deficits were mild in most patients, but neuropsychological testing demonstrated cognitive deficits in all patients. Depression and anxiety were common. Although most patients thought that their social functioning and work ability were impaired, little reduction in overall quality of life was perceived.