Michael D. Jenkinson

‘Recurrent’ glioblastoma multiforme, when should we reoperate?

The surgical management of recurrent glioblastoma multiforme is controversial. Recent publications suggest that re-operation provides 3–5 months median survival, without significant increases in morbidity or martality. Age (≤50 years, although older patients may also benefit) and performance status (Karnofsky performance score ≥60–70) are the most important factors. Reresection not only improves symptoms and maintains quality of life, it can delay symptom progression, reduce corticosteroid doses, and also improve response to (and allow intra-operative) chemotherapy and/or radiotherapy. Surgical treatment of recurrent glioblastoma multiforme in selected patients should always be considered.

Management of cerebral metastasis: Evidence-based approach for surgery, stereotactic radiosurgery and radiotherapy

Brain metastases constitute a significant disease burden and have a major impact on morbidity and mortality. This review discusses the relative merits of open surgery, whole brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS), which have been used alone and in combination with varying degrees of success for the treatment of newly diagnosed brain metastasis. Treatment aims to provide disease control with a good quality of life, although prolonged survival may not always be achieved. Decision to treat is based on several prognostic factors including age, performance status and control of the primary cancer. The recently developed disease-specific graded prognostic assessment (DS-GPA) scales can aid in clinical decision making for individual patients. Whole brain radiotherapy remains the mainstay of treatment and provides effective palliation. Omission of WBRT results in worse local and distant control, though not survival. Local tumour control can be achieved by either resection of stereotactic radiosurgery (SRS). In long-term survivors WBRT may cause cognitive decline and SRS is being explored as an alternative method of disease control. Increasingly, quality of life and neuro-cognitive function are being used as end-points in clinical trials.

The role of endoscopic third ventriculostomy in adult patients with hydrocephalus.

OBJECT Endoscopic third ventriculostomy (ETV) is the treatment of choice for hydrocephalus, but the outcome is dependent on the cause of this disorder, and the procedure remains principally the preserve of pediatric neurosurgeons. The role of ETV in adult patients with hydrocephalus was therefore investigated. METHODS One hundred ninety adult patients underwent ETV for hydrocephalus. Cases were defined as primary ETV (newly diagnosed, without a previously placed shunt) and secondary ETV (performed for shunt malfunctions due to infection or mechanical blockage). Causes of hydrocephalus included tumor, long-standing overt ventriculomegaly (LOVA), Chiari malformation Types I and II (CM-I and -II), aqueduct stenosis, spina bifida, and intraventricular hemorrhage (IVH). Successful ETV was defined as resolution of symptoms with shunt independence. Operative complications and ETV failure rate were investigated according to the causes of hydrocephalus and between the primary and secondary ETV groups. RESULTS In the primary group, ETV was successful in 107 (83%) of 129 patients, including those with tumors (52 of 66), LOVA (21 of 24), CM-I (11 of 11 cases), CM-II (8 of 9), aqueduct stenosis (8 of 9), and IVH (2 of 2). In the secondary group, ETV was successful in 41 (67%) of 61 patients and was equally successful in cases of mechanical shunt malfunction (35 of 52 patients) and infected shunt malfunction (6 of 9 patients). The median time to ETV failure was 1.7 months in the primary group and 0.5 months in the secondary group. The majority of ETV failures occurred within the first 3 months, and thereafter, the Kaplan-Meier survival curves plateaued. There were no procedure-related deaths, and complications were seen in only 5.8% of cases. CONCLUSIONS The success rate of ETVs in adults is comparable, if not better, than in children. In addition to the well-defined role of ETV in the treatment of hydrocephalus caused by tumors and aqueduct stenosis, ETV may also have a role in the management of CM-I, LOVA, persistent shunt infection, and IVH resistant to other CSF diversion procedures.

Cerebral blood volume, genotype and chemosensitivity in oligodendroglial tumours.

IntroductionThe biological factors responsible for differential chemoresponsiveness in oligodendroglial tumours with or without the −1p/−19q genotype are unknown, but tumour vascularity may contribute. We aimed to determine whether dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) could distinguish molecular subtypes of oligodendroglial tumour, and examined the relationship between relative cerebral blood volume (rCBV) and outcome following procarbazine, lomustine and vincristine (PCV) chemotherapy.MethodsPretherapy rCBV was calculated and inter- and intraobserver variability assessed. Allelic imbalance in 1p36, 19q13, 17p13, 10p12–15, and 10q22–26 and p53 mutation (exons 5–8) were determined. rCBV was compared with genotype and clinicopathological characteristics (n=37) and outcome following PCV chemotherapy (n=33).Results1p/19q loss was seen in 6/9 grade II oligodendrogliomas, 6/14 grade II oligoastrocytomas, 4/4 grade III oligodendrogliomas, and 3/10 grade III oligoastrocytomas. rCBV measurements had good inter- and intraobserver variability, but did not distinguish histology subtype or grade. Tumours with 1p/19q loss had higher rCBV values (Student’s t-test P=0.001). Receiver operating characteristic analysis revealed a cut-off of 1.59 for identifying genotype (sensitivity 92%, specificity 76%). Tumours with high and low rCBV showed response to chemotherapy. The −1p/−19q genotype, but not rCBV, was strongly associated with response, progression-free and overall survival following PCV chemotherapy. Tumours with high rCBV and intact 1p/19q were associated with shorter progression-free and overall patient survival than those with intact 1p/19q and low rCBV or high rCBV and 1p/19q loss.ConclusionrCBV identifies oligodendroglial tumours with 1p/19q loss, but does not predict chemosensitivity. The prognostic significance of rCBV may differ in oligodendroglial tumours with or without the −1p/−19q genotype.

Effect of electromagnetic-navigated shunt placement on failure rates: a prospective multicenter study.

OBJECT As many as 40% of shunts fail in the first year, mainly due to proximal obstruction. The role of catheter position on failure rates has not been clearly demonstrated. The authors conducted a prospective cohort study of navigated shunt placement compared with standard blind shunt placement at 3 European centers to assess the effect on shunt failure rates. METHODS All adult and pediatric patients undergoing de novo ventriculoperitoneal shunt placement were included (patients with slit ventricles were excluded). The first cohort underwent standard shunt placement using anatomical landmarks. All centers subsequently adopted electromagnetic (EM) navigation for routine shunt placements, forming the second cohort. Catheter position was graded on postoperative CT in both groups using a 3-point scale developed for this study: (1) optimal position free-floating in CSF; (2) touching choroid or ventricular wall; or (3) intraparenchymal. Episodes and type of shunt revision were recorded. Early shunt failure was defined as that occurring within 30 days of surgery. Patients with shunts were followed-up for 12 months in the standard group, for a median of 6 months in the EM-navigated group, or until shunt failure. RESULTS A total of 75 patients were included in the study, 41 with standard shunts and 34 with EM-navigated shunts. Seventy-four percent of navigated shunts were Grade 1 compared with 37% of the standard shunts (p=0.001, chi-square test). There were no Grade 3 placements in the navigated group, but 8 in the standard group, and 75% of these failed. Early shunt failure occurred in 9 patients in the standard group and in 2 in the navigated group, reducing the early revision rate from 22 to 5.9% (p=0.048, Fisher exact test). Early shunt failures were due to proximal obstruction in 78% of standard shunts (7 of 9) and in 50% of EM-navigated shunts (1 of 2). CONCLUSIONS Noninvasive EM image guidance in shunt surgery reduces poor shunt placement, resulting in a significant decrease in the early shunt revision rate.

Advanced MRI in the management of adult gliomas

Gliomas are a heterogeneous group that account for ∼86% of primary brain neoplasms, and include astrocytic and oligodendroglial tumours, as well as a variety of less common histopathological subtypes. Magnetic resonance imaging has become the accepted mode of imaging for the clinical management of these tumours. MRI features bear close resemblance to the histopathology grading and prognosis of these tumours. Currently, conventional MRI is used to aid diagnosis, plan neurosurgical approaches, and monitor response to therapy and disease progression. More recent developments in the field of MRI include MR spectroscopy, perfusion MRI, diffusion-weighted imaging, intraoperative MRI and functional MRI. These newer techniques have been adopted with varying success in the management of adult gliomas. This review focuses on the application of advanced MR imaging in the clinical management of adult gliomas.

Apparent diffusion coefficients in oligodendroglial tumors characterized by genotype.

To investigate whether oligodendroglial tumors with or without 1p/19q loss differ in their diffusion‐weighted imaging characteristics. Oligodendroglial tumors with or without 1p/19q loss differ in their therapeutic responsiveness and prognosis, and recent reports also suggest that these tumors may differ in their magnetic resonance characteristics and blood volume.

Correlation of Molecular Genetics with Molecular and Morphological Imaging in Gliomas with an Oligodendroglial Component

Purpose: Since the recognition that oligodendrogliomas may be chemosensitive, their diagnosis and clinical management has become highly controversial. Histopathology diagnosis remains challenging and new tools such as molecular genetics or molecular imaging require evaluation. Experimental Design: In a single-center, population-based prospective study, allelic imbalance in chromosomes 1p36, 19q13, 17p13, 10p12–15, and 10q22–26 has been investigated in 19 oligodendroglioma WHO grade 2 (OII), 20 oligoastrocytoma WHO grade 2 (OAII), 8 oligodendroglioma WHO grade 3 (OIII), and 12 oligoastrocytoma WHO grade 3 (OAIII), and compared with pretherapy histopathology, computed tomography and/or magnetic resonance (CT and/or MR), [fluorine-18]fluoro-2-deoxyglucose (18F-FDG), and thallium-201 single-photon emission computed tomography (201Tl SPECT). Results: In 50 cases, 18F-FDG uptake correlated with 201Tl uptake; however, 8 cases had increased 201Tl uptake but were hypometabolic for 18F-FDG, and 1 case was hypermetabolic with normal 201Tl uptake. Sixteen cases enhanced on CT/MR but failed to show 201Tl uptake; and 2 low-grade non-enhancing oligodendrogliomas had increased 201Tl uptake. Increased metabolism was more likely in high-grade cases, with 201Tl uptake more strongly correlated with grade than was 18F-FDG uptake. Tumors with 1p/19q loss were more likely to show increased 201Tl uptake and, to a lesser degree, increased 18F-FDG uptake than those without these losses. Elevated metabolism in 28% of low-grade tumors was significantly more common in tumors with 1p/19q loss, and increased uptake of both 18F-FDG and 201Tl in low-grade cases was found only in those with 1p/19q loss. Conclusions: In this study, dissociation of uptake of contrast agents and radiotracers suggests independent deregulation of the blood–brain barrier breakdown and metabolism during disease progression of oligodendroglial neoplasms, and the association of elevated metabolism with 1p/19q loss, particularly in low-grade tumors, may have implications for clinical management.

EANO guidelines for the diagnosis and treatment of meningiomas

Although meningiomas are the most common intracranial tumours, the level of evidence to provide recommendations for the diagnosis and treatment of meningiomas is low compared with other tumours such as high-grade gliomas. The meningioma task force of the European Association of Neuro-Oncology (EANO) assessed the scientific literature and composed a framework of the best possible evidence-based recommendations for health professionals. The provisional diagnosis of meningioma is mainly made by MRI. Definitive diagnosis, including histological classification, grading, and molecular profiling, requires a surgical procedure to obtain tumour tissue. Therefore, in many elderly patients, observation is the best therapeutic option. If therapy is deemed necessary, the standard treatment is gross total surgical resection including the involved dura. As an alternative, radiosurgery can be done for small tumours, or fractionated radiotherapy in large or previously treated tumours. Treatment concepts combining surgery and radiosurgery or fractionated radiotherapy, which enable treatment of the complete tumour volume with low morbidity, are being developed. Pharmacotherapy for meningiomas has remained largely experimental. However, antiangiogenic drugs, peptide receptor radionuclide therapy, and targeted agents are promising candidates for future pharmacological approaches to treat refractory meningiomas across all WHO grades.

MRS of oligodendroglial tumors Correlation with histopathology and genetic subtypes

Background: Oligodendroglial neoplasms with combined loss of chromosomes 1p and 19q may have a good prognosis and respond to procarbazine-lomustine (CCNU)-vincristine (PCV) chemotherapy. Objective: To determine whether single voxel magnetic resonance spectroscopy (SV-MRS) obtained through routine clinical practice distinguishes between histopathologic and genetic subtypes of oligodendroglial tumors. Methods: Forty-eight patients with oligodendroglial tumors (19 oligodendrogliomas and 29 oligoastrocytomas) underwent molecular genetic analysis to determine allelic imbalance in chromosomes 1p36 and 19q13. SV-MRS was obtained pretherapy to determine tumor metabolite ratios. Results: Grade III oligodendroglial tumors had higher choline (Mann–Whitney; p = 0.002), methyl lipid (Mann–Whitney; p = 0.002), and combined methylene lipid and lactate ratios (Mann–Whitney; p < 0.001) than grade II tumors. Lactate did not distinguish between tumor types (Fisher exact test; p = 0.342) or grade (Fisher exact test; p = 0.452). There were no significant associations when tumors were analyzed according to histopathology or genetic subtypes. Conclusion: As a noninvasive diagnostic tool used in routine clinical practice, SV-MRS has the potential benefit of determining oligodendroglial tumor grade but not subtypes classified by histopathology or molecular genetics. MRS may be useful for determining the timing of therapy but is unlikely to predict chemosensitivity.