Role of adjuvant radiotherapy in atypical (WHO grade II) and anaplastic (WHO grade III) meningiomas: a systematic review

The systematic adoption of the histopathologic criteria provided by the 2016 update of the WHO classification of brain tumors has markedly increased the relative proportion of atypical and anaplastic meningiomas. These tumors exhibit a much greater recurrence rate compared to benign meningiomas, which negatively impacts survival. In recent years, the publication of numerous retrospective case series, yet no randomized controlled trials, on the impact of radiation therapy in non-benign meningioma, has yielded conflicting evidence. At present, maximum safe resection, including the dural attachment, is the preferred primary treatment modality for all types of meningiomas. Adjuvant radiotherapy is currently recommended for subtotally resected grade II and for all grade III meningiomas. However, in grade II meningiomas achieving complete resection, close radiologic and clinical observation is a feasible option. Despite the great amount of non-benign meningiomas available and eligible for trials, there is a striking lack of prospective studies testing adjuvant therapies against observation for this subset of patients. An updated and systematic literature review is provided on the effectiveness and indications of radiotherapy on grade II and III meningiomas (AU)

Role of adjuvant radiotherapy in atypical (WHO grade II) and anaplastic (WHO grade III) meningiomas: a systematic review.

The systematic adoption of the histopathologic criteria provided by the 2016 update of the WHO classification of brain tumors has markedly increased the relative proportion of atypical and anaplastic meningiomas. These tumors exhibit a much greater recurrence rate compared to benign meningiomas, which negatively impacts survival. In recent years, the publication of numerous retrospective case series, yet no randomized controlled trials, on the impact of radiation therapy in non-benign meningioma, has yielded conflicting evidence. At present, maximum safe resection, including the dural attachment, is the preferred primary treatment modality for all types of meningiomas. Adjuvant radiotherapy is currently recommended for subtotally resected grade II and for all grade III meningiomas. However, in grade II meningiomas achieving complete resection, close radiologic and clinical observation is a feasible option. Despite the great amount of non-benign meningiomas available and eligible for trials, there is a striking lack of prospective studies testing adjuvant therapies against observation for this subset of patients. An updated and systematic literature review is provided on the effectiveness and indications of radiotherapy on grade II and III meningiomas.

Central nervous system ependymoma: clinical implications of the new molecular classification, treatment guidelines and controversial issues.

Ependymoma is an uncommon neuroepithelial tumor that may arise anywhere within the neuroaxis, both in children and in adults. It has been classically graded upon histopathological features, yet with limited clinical utility. Recently, DNA methylation profiling has provided a novel classification of ependymoma in nine molecular subgroups. This stratification method harbors prognostic value with supratentorial RELA-fusion and posterior fossa group A tumors showing a significantly shorter survival compared to the rest. Currently, the treatment of choice involves maximal safe resection and, in cases of residual disease, adjuvant conformal radiotherapy. Second-look surgery is also a feasible and recommended option for incompletely resected tumors. The role of chemotherapy is not yet established and can be considered in infants and children with relapsing disease or prior to re-intervention. Although targeted agents do not seem to play a role as adjuvant therapy, they are currently being tested for recurrent disease.

Treatment-related changes in glioblastoma: a review on the controversies in response assessment criteria and the concepts of true progression, pseudoprogression, pseudoresponse and radionecrosis.

The assessment of response to therapy in glioblastoma remains a challenge, because the surrogate measures of survival are subject to radiographic misinterpretation. A solid and reliable definition of progression is needed for both clinical decision-making and for evaluating response within the clinical trials. Historically, assessment criteria have used radiologic and clinical features aimed to correctly classify patients into progressive or non-progressive disease. The widely used RANO criteria are a valuable tool in disease evaluation, both in the clinical setting and in the clinical trials. However, assessment criteria have certain limitations that emerging image techniques have tried to overcome. Differentiating true progression from treatment-related changes (like pseudoprogression or pseudoresponse) is crucial in order not to prematurely discontinue adjuvant chemotherapy or redirect the patient to second-line options. This fact underscores the need for advanced radiologic techniques, like specific diffusion and perfusion MRI sequences, MR spectroscopy and PET, which seem to play a role in distinguishing these phenomena.

Diffuse low-grade glioma: a review on the new molecular classification, natural history and current management strategies.

The management of diffuse supratentorial WHO grade II glioma remains a challenge because of the infiltrative nature of the tumor, which precludes curative therapy after total or even supratotal resection. When possible, functional-guided resection is the preferred initial treatment. Total and subtotal resections correlate with increased overall survival. High-risk patients (age >40, partial resection), especially IDH-mutated and 1p19q-codeleted oligodendroglial lesions, benefit from surgery plus adjuvant chemoradiation. Under the new 2016 WHO brain tumor classification, which now incorporates molecular parameters, all diffusely infiltrating gliomas are grouped together since they share specific genetic mutations and prognostic factors. Although low-grade gliomas cannot be regarded as benign tumors, large observational studies have shown that median survival can actually be doubled if an early, aggressive, multi-stage and personalized therapy is applied, as compared to prior wait-and-see policy series. Patients need an honest long-term therapeutic strategy that should ideally anticipate neurological, cognitive and histopathologic worsening.

Survival in glioblastoma: a review on the impact of treatment modalities.

Glioblastoma (GBM) is the most common and lethal tumor of the central nervous system. The natural history of treated GBM remains very poor with 5-year survival rates of 5 %. Survival has not significantly improved over the last decades. Currently, the best that can be offered is a modest 14-month overall median survival in patients undergoing maximum safe resection plus adjuvant chemoradiotherapy. Prognostic factors involved in survival include age, performance status, grade, specific markers (MGMT methylation, mutation of IDH1, IDH2 or TERT, 1p19q codeletion, overexpression of EGFR, etc.) and, likely, the extent of resection. Certain adjuncts to surgery, especially cortical mapping and 5-ALA fluorescence, favor higher rates of gross total resection with apparent positive impact on survival. Recurrent tumors can be offered re-intervention, participation in clinical trials, anti-angiogenic agent or local electric field therapy, without an evident impact on survival. Molecular-targeted therapies, immunotherapy and gene therapy are promising tools currently under research.

Metastatic meningioma to the eleventh dorsal vertebral body: total en bloc spondylectomy. Case report and review of the literature

Introducción. Las metástasis distantes de meningioma intracraneal ocurren en uno de cada milmeningiomas. La mayor parte afectan a pulmón u órganos intraabdominales. Sólo un 7% aparecen en vértebras. Se han publicado en torno a una docena de casos. Presentamos la primera descripción hasta la fecha de una vertebrectomía completa por vía posterior para tratar una metástasis intraósea de meningioma benigno en el cuerpo de T11.Caso clínico. Varón de 37 años de edad, intervenido en otro centro en Marzo de 1996 de meningioma benigno intraventricular occipital izquierdo de tipo transicional(OMS tipo I). Precisó reintervención por recidiva local en Febrero de 2002. A finales de 2003 comenzó con dolor dorso lumbar intenso y el estudio de RM espinal evidenció una masa intrósea en T11. En Marzo de 2004se realizó biopsia transpedicular y vertebroplastia acrílica. El resultado histológico fue de adenocarcinoma y el paciente comenzó a recibir quimioterapia. Una segunda opinión sobre las muestras histológicas sugirió el diagnóstico de meningioma. El estudio de extensión tumoral no evidenció otra neoplasia primaria. En Mayo de 2004 ingresó en nuestro servicio donde se repite la biopsia transpedicular que confirma el diagnóstico de meningioma. En Junio de 2004 se realizó vertebrectomíaT11 completa por vía posterior, según técnica de Tomita, artrodesis intersomática con cajas apilables de fibra de carbono rellenas de injerto óseo y sustituto cálcico, y fijación transpedicular T9 a L1. La evolución postoperatoria fue satisfactoria y, actualmente, se encuentra libre de enfermedad primaria y secundaria. Anatomía patológica definitiva: meningioma benigno(OMS I).Discusión. Las metástasis distantes de meningiomas intracraneales son entidades raras que en más del 60%de los casos provienen de meningiomas benignos. Enamy cols diseñaron una gradación según parámetros histológicos para diferenciar los meningiomas benignos e los atípicos y malignos. Dicha gradación correlaciona con la probabilidad de producir metástasis distantes: más del 40% en los meningiomas malignos frente a una media del 3.8% de todos los tumores cerebrales. La posibilidad de metastatizar parece relacionarse con la capacidad de invasividad vascular o linfática. Las metástasis son más frecuentes en las variantes angioblástica, papilar y meningotelial. Se describen tres vías de diseminación: hematógena (sobre todo venosa; plexo perivertebral de Batson) linfática y por LCR. La craneotomía podría ser otra vía de diseminación pues la mayoría de los pacientes han sido previamente multioperados del tumor craneal. El tiempo transcurrido entre el diagnóstico del meningioma intracraneal y la aparición de la metástasis vertebral puede variar entremeses y años. La rentabilidad diagnóstica de la biopsia transpedicular es mayor del 80% y mejora cuanto mayor es el diámetro interno de la trefina utilizada. En el caso descrito, aplicamos el concepto oncológico de resección en bloque de la vértebra afectada. Creemos que se trata de una indicación paradigmática de esta técnica pues respeta los conceptos de resección radical y estabilidad de la columna, y otorga una oportunidad de curación de la enfermedad

Introduction. One in every thousand intracranial meningiomas metastatize extracranially. Lung andintra abdominal organs are most frequently affected. Only 7% involve vertebrae and just a dozen cases have been reported in the literature. To our knowledge, this is the first description of a total en bloc spondylectomy through a posterior approach for the treatment of an intraosseous metastatic meningioma to the eleventh dorsal vertebra. Case report. In March 1996, a 37 year-old male underwent surgical resection for a left occipital intraventricular benign meningioma (WHO I). He wasreoperated in February 2002 due to local recurrence. By the end on 2003 he developed progressively invalidating dorso lumbar pain. MRI studies revealed a T11 intraosseous mass. In March 2004, a percutaneous biopsy and vertebroplasty were performed. The pathological specimen was identified as adenocarcinoma and he initiated chemotherapy. Advice from a second pathologist was seeked, who suggested the diagnosis of intraosseous meningioma. Workup studies failed to reveal any primary tumor. In May 2004 the patient was admitted to our department and a new transpedicular biopsy confirmed the diagnosis. In June 2004 he underwentT11 total en bloc spondylectomy (Tomita's procedure),fusion with bone and calcium substitute-filled stackable carbon-fiber cages, and T9 to L1 transpedicular screw fixation. No postoperative complications ocurred and he is, so far, free from primary and secondary disease. Definite pathology: benign meningioma (WHO I).Discussion. Distant metastases from intracranial meningioma’s are rare entities, arising from benign lesions in, at least, 60% of cases. En am et al proposed a specific pathological score to differentiate benign, atypic and malignant meningiomas. Such score correlates with the chance of metastatizing: more than 40%in malignant meningiomas compared to 3.8% of brain tumors overall. The ability to metastatize seems to be linked to vascular or lifatic invasiveness. Metastases ocurr more frequently in angioblastic, papillary and meningothelial variants. Hematogenous (especially venous; Batson's perivertebral plexus), linfatic and cerebrospinal fluid are the main routes involved in the spreading of the tumor. Craniotomy itself may also play a role, for the majority of patients have been previously operated on repeatedly. The interval between the onset of the intracranial disease and the appearance of the metastasis varies from months to many years. The value of transpedicular biopsy is widely recognized (efficacy over 80%) and the suitability of the specimen for pathological examination improves when wide inner caliber trephines are used. In the case presented we applied the oncologic concept of vertebral en bloc resection. We believe this case represents a paradigmatic indication of this technique because it respects the concepts of radical resection and spinal stability, and offers an opportunity for the curation of the disease