Winst en verlies: een balans van 15 jaar neuro-oncologie in Rotterdam

Rede, in verkorte vorm uitgesproken ter gelegenheid van het aanvaarden van het ambt van bijzonder hoogleraar in de Neuro-Oncologie aan het Erasmus MC, faculteit van de Erasmus Universiteit Rotterdam op 19 januari 200

Het gebruik van polymethylmethacrylaat bij de cervicale anterieure discectomie

In veel klinieken worden patienten die veor operatie veor een cervicaal radiculair syndroom door discuspathologie in aanmerking komen behandeld met een of andere variant van de anterieure cervicale discectomie. In het Sint Lucas Ziekenhuis te Amsterdam gebeurde dit tot eind 1984 door anterieure discectomie gevolgd door fusie met autoloog bot. Daarbij wordt na het uitruimen van de discus een bottransplantaat, verkregen uit de bekkenkam van tussenwervelruimte gebracht zodat een benige vergroeiing tussen wervellichamen ontstaat. de patient, in de de aangrenzende Vanaf 1985 werd in plaats van bot 'botcement' of weI polymethylmethacrylaat (PMMA) in de uitgeruimde tussenwervelruimte ingebracht. Het doe! van deze wijziging was: - het vermijden van postoperatieve pijnklachten ter plaatse van de bekkenkam doordat uitname van een transplantaat niet meer plaatsvond - het verkrijgen van een snelle immobilisering van het geopereerde segment, zodat het niet langer noodzakelijk zou zijn de cervica1e wervelkolom van de patienten tijdelijk te immobiliseren met een gipskraag. Dit werd na het inbrengen van een bottransplantaat weI wenselijk geacht, teneinde een goede fusie te verkrijgen. Besloten werd deze wijziging te evalueren. Hiervoor is in eerste instantie een retrospectief onderzoek verricht naar de resultaten van de anterieure discectomie met fusie met autoloog bot. (8) Daarna is een prospectief onderzoek gestart naar de resultaten van anterieure discectomie gevolgd door interpositie van PMMA. Omdat uit een aantal studies was gebleken cIat resultaten van discectomie zonder fusie gelijkwaardig waren aan die van discectomie met fusie (87.91. 116), is besloten het effect van discectomie met het inbrengen van PMMA te vergelijken met een controlegroep die met alleen discectomie was behandeld. Daarbij is gekozen voor een gerandomiseerde opzet, met beoordeling van het resultaat door een onafhankelijke beoordelaar. Het onderzoek moet een antwoord geven op de volgende vragen: 1) Verbetert het klinisch resultaat van de anterieure discectomie als behandeling van een cervicaal radiculair syndroom door een discusprolaps of door osteofyten indien hierna PMMA wordt ingebracht in de uitgeruimde tussenwervelschijf? Maakt het inbrengen van PMMA verschil voor wat betreft het persisteren of ontstaan van nekklachten na de ingreep? 2) Is er bij radiologisch naonderzoek een verschil zichtbaar tussen beide groepen in het optreden of de progressie van degeneratieve afwijkingen in de aangrenzende segmenten? Voldoet PMMA vanuit radiologisch perspectief aan de doelstellingen van het inbrengen van een implantaat

How I treat anaplastic glioma without 1p/19q codeletion

Anaplastic astrocytoma without 1p/19q codeletion is a rare primary central nervous system tumour occurring primarily in middle-aged adults and associated with a median survival of 5–10 years. The major corner stone of treatment is maximal safe neurosurgical resection, followed by radiotherapy and chemotherapy. Several clinical trials addressed the optimal adjuvant treatment; however, interpretation has been challenged by the recent molecular marker-based reclassification of tumour. The interim study of the CATNON trial strongly suggests the addition of 12 adjuvant cycles of temozolomide in addition to radiotherapy after maximal safe resection in patients with anaplastic astrocytoma without 1p/19q codeletion. Based on more recently presented data from the second interim analysis of the CATNON trial and from the molecular analysis, benefit from temozolomide during and after radiotherapy is limited to patients with isocitrate dehydrogenase-mutated anaplastic astrocytoma. Given the small patient number in the single subgroups and the so far missing neurocognitive and quality of life data, more mature analyses needs to be awaited to draw final conclusions on the application of concurrent temozolomide treatment for the daily routine in patients who already are scheduled for adjuvant temozolomide. Further molecular analysis is ongoing to define personalised treatment approaches in patients with anaplastic astrocytom

Detection of 1p19q Deletion by Real-Time Comparative Quantitative PCR

1p/19q (1p and/or 19q) deletions are prognostic factors in oligodendroglial tumors (OT) and predict better survival after both chemotherapy and radiotherapy. While studying 1p/19q status as a potential variable within multivariate prognosis models for OT, we have frequently encountered unknown 1p/19q status within our glioma sample database due to lack of paired blood samples for loss of heterozygosity (LOH) assay and/or failure to perform fluorescence in situ hybridization (FISH). We realized that a 1p and 19q deletion assay that could be reliably performed solely on tumor DNA samples would allow us to fill in these molecular biology data “holes”. We built recombinant DNA with fragments of the selected “marker” genes in 1p (E2F2, NOTCH2), and 19q (PLAUR) and “reference” genes (ERC2, SPOCK1, and SPAG16 ) and used it as quantification standard in real-time PCR to gain absolute ratios of marker/reference gene copy numbers in tumor DNA samples, thus called comparative quantitative PCR (CQ-PCR). Using CQ-PCR, we identified 1p and/ or 19q deletions in majority of pure low-grade oligodenroglioma (OG) tumors (17/21, 81%), a large portion of anaplastic oligodendroglioma (AO) tumors (6/15, 47%), but rarely found in mixed oligoastrcytomas (OA) tumors (1/8, 13%). These data are consistent with results of LOH and FISH assays generally reported for these tumor types. In addition, 15 out 18 samples showed concordant results between FISH and CQ-PCR. We conclude that CQ-PCR is a potential means to gain 1p/19q deletion information, which prognostic and predictive values of CQ-PCR-derived 1p/19q status will be determined in a future study

Association Between Supratotal Glioblastoma Resection and Patient Survival: A Systematic Review and Meta-Analysis

- BACKGROUND: Gross total resection (GTR) of the contrast enhancing (CE) area will improve the survival of patients with glioblastoma (GBM). However, GBM can infiltrate into the brain parenchyma, beyond the CE margins. It remains unclear whether resection beyond the CE area (supratotal resection [SPTR]) can improve survival without causing additional neurological deficits. The aim of the present meta-analysis was to study the association between SPTR and overall survival of patients of GBM. - METHODS: Embase, PubMed, and other literature databases were searched for eligible studies until August 2018. Studies involving patients with GBM that had compared SPTR with GTR were included in the present study. The main outcome was overall survival, presented as hazard ratios (HRs) with 95% confidence intervals (CIs) and median overall survival differences with the 95% CIs. - RESULTS: The meta-analysis, which included 6 studies and 1168 unique patients with GBM, showed that compared with GTR, SPTR of GBM resulted in a 53% lower risk of mortality at any time during follow-up (HR, 0.47; 95% CI, 0.31e 0.72; P [ 0.0005). The median overall survival of the SPTR group was 6.4 months (95% CI, 3.2e9.7) longer than the GTR group (P [ 0.0001). Reports on postoperative deficits were limited, and the quality of evidence was moderate to very low. - CONCLUSIONS: Compared with GTR, SPTR of GBM resulted in a lower risk of mortality and longer median overall survival. However, the quality of evidence of the available studies was poor. Therefore, it remains unclear whether SPTR is safe and actually improves the survival of patients with GBM. Future prospective trials and a standardized definition of SPTR are needed

Pleural metastasis of anaplastic meningioma

A 52-year-old woman presented to the emergency department with several days of progressive dyspnoea and thoracic pain. Her medical history included a (recurrent) anaplastic meningioma, for which she was treated with surgery and radiotherapy. A chest X-ray showed occurrence of total opacification of the left lower lobe and a chest computed tomography demonstrated a pleural mass of 12 × 9 × 15 cm in the left lower lobe. Biopsy of the pleural mass revealed a metastasis of the patient’s anaplastic meningioma. Extracranial metastases from meningioma are extremely uncommon (≤ 0.1%-0.2% of cases), but important for a patient’s prognosis

How we treat patients with leptomeningeal metastases

The goal of treatment of leptomeningeal metastasis is to improve survival and to maintain quality of life by delaying neurological deterioration. Tumour-specific therapeutic options in

Current treatment of low grade gliomas

Low grade gliomas affect predominantly young adults, and have a relatively favorable prognosis compared to grade III and grade IV gliomas. The challenge for an optimal management of these patients is to find the balance between an optimal survival and the preservation of neurological function including cognition. Because all medical treatments may induce side effects, in young and nearly asymptomatic patients the choices can be difficult. This review summarizes the current strategies: a watch-and-wait policy, surgery, chemotherapy, and radiotherapy

Pseudoprogression of brain tumors

This review describes the definition, incidence, clinical implications, and magnetic resonance imaging (MRI) findings of pseudoprogression of brain tumors, in particular, but not limited to, high-grade glioma. Pseudoprogression is an important clinical problem after brain tumor treatment, interfering not only with day-to-day patient care but also the execution and interpretation of clinical trials. Radiologically, pseudoprogression is defined as a new or enlarging area(s) of contrast agent enhancement, in the absence of true tumor growth, which subsides or stabilizes without a change in therapy. The clinical definitions of pseudoprogression have been quite variable, which may explain some of the differences in reported incidences, which range from 9-30%. Conventional structural MRI is insufficient for distinguishing pseudoprogression from true progressive disease, and advanced imaging is needed to obtain higher levels of diagnostic certainty. Perfusion MRI is the most widely used imaging technique to diagnose pseudoprogression and has high reported diagnostic accuracy. Diagnostic performance of MR spectroscopy (MRS) appears to be somewhat higher, but MRS is less suitable for the routine and universal application in brain tumor follow-up. The combination of MRS and diffusion-weighted imaging and/or perfusion MRI seems to be particularly powerful, with diagnostic accuracy reaching up to or even greater than 90%. While diagnostic performance can be high with appropriate implementation and interpretation, even a combination of techniques, however, does not provide 100% accuracy. It should also be noted that most studies to date are small, heterogeneous, and retrospective in nature. Future improvements in diagnostic accuracy can be expected with harmonization of acquisition and postprocessing, quantitative MRI and computer-aided diagnostic technology, and meticulous evaluation with clinical and pathological data