Cancer Registration, Molecular Marker Status, and Adherence to the WHO 2016 Classification of Pathology Reports for Glioma Diagnosed during 2017-2019 in Belgium.

INTRODUCTION: The objective of this study was to cross-check and, if necessary, adjust registered ICD-O-3 topography and morphology codes with the findings in pathology reports available at the Belgian Cancer Registry (BCR) for glioma patients. Additionally, integration of molecular markers in the pathological diagnosis and concordance with WHO 2016 classification is investigated. METHODS: Since information regarding molecular tests and corresponding conclusions are not available as structured data at population level, a manual screening of all pseudonymized pathology reports available at the BCR for registered glioma patients (2017-2019) was conducted. ICD-O-3 morphology and topography codes from the BCR database (based on information as provided by hospital oncological care programmes and pathology laboratories), were, at tumour level, cross-checked with the data from the pathology reports and, if needed, specified or corrected. Relevant molecular markers (IDH1/2, 1p19q codeletion, promoter region of the MGMT gene [MGMTp]) were manually extracted from the pathology reports. RESULTS: In 95.3% of gliomas, the ICD-O-3 morphology code was correct. Non-specific topography codes were specified in 9.3%, while 3.3% of specific codes were corrected. The IDH status was known in 75.2% of astrocytic tumours. The rate of correct integrated diagnoses varied from 47.6% to 56.4% among different gliomas. MGMTp methylation status was available in 32.2% of glioblastomas. CONCLUSION: Both the integration of molecular markers in the conclusion of the pathology reports and the delivery of those reports to the BCR can be improved. The availability of distinct ICD-O-3 codes for each molecularly defined tumour entity within the WHO classification would increase the consistency of cancer registration, facilitate population level research and international benchmarking.

Quality indicators in neuro-oncology: Review of the literature and development of a new quality indicator set for glioma care through a two-round Delphi survey.

BACKGROUND: Quality Indicators (QIs) are important tools to assess the quality and variability of oncological care. However, their application in neuro-oncology is limited so far. The objective of this study was to develop a set of QIs for glioma, covering process and outcome indicators. METHODS: A systematic review was conducted to identify both QIs in the field of adult glioma care, and guidelines or recommendations that could be translated into QIs. Also reports from national and international healthcare agencies and scientific associations ("grey literature") were taken into account. After conversion of these recommendations into QIs, merging with existing QIs found in the literature and rationalization, a two-round Delphi survey was conducted to gain consensus on relevance for the proposed QIs. RESULTS: In total 240 recommendations and 30 QIs were retrieved from the literature. After conversion, merging and rationalization, 147 QIs were evaluated in the Delphi survey and eventually consensus was gained on 47 QIs in the following 7 domains: Diagnosis and Imaging, Surgery, Pathology, Radio/Chemotherapy, Recurrence, Supportive Treatments (Epilepsy, Thromboembolism, Steroid Use and Rehabilitation) and Survival. CONCLUSION: This study defined a set of 47 QIs for assessing quality of care in adult glioma patients, distributed amongst 7 crucial phases in the patient's care trajectory. These QIs are readily applicable for use in diverse health care systems, depending on the availability of population-based health care data enabling (inter)national benchmarking.

The supplementary motor area syndrome: a neurosurgical review.

The supplementary motor area (SMA) syndrome is a frequently encountered clinical phenomenon associated with surgery of the dorsomedial prefrontal lobe. The region has a known motor sequencing function and the dominant pre-SMA specifically is associated with more complex language functions; the SMA is furthermore incorporated in the negative motor network. The SMA has a rich interconnectivity with other cortical regions and subcortical structures using the frontal aslant tract (FAT) and the frontostriatal tract (FST). The development of the SMA syndrome is positively correlated with the extent of resection of the SMA region, especially its medial side. This may be due to interruption of the nearby callosal association fibres as the contralateral SMA has a particular important function in brain plasticity after SMA surgery. The syndrome is characterized by a profound decrease in interhemispheric connectivity of the motor network hubs. Clinical improvement is related to increasing connectivity between the contralateral SMA region and the ipsilateral motor hubs. Overall, most patients know a full recovery of the SMA syndrome, however a minority of patients might continue to suffer from mild motor and speech dysfunction. Rarely, no recovery of neurological function after SMA region resection is reported.

Survival impact of incidental subventricular zone irradiation in IDH-wildtype glioblastoma.

BACKGROUND AND PURPOSE: The subventricular zone (SVZ) is an important niche for neural stem cells but probably also for brain tumor propagating cells, including the glioblastoma stem cell. The SVZ may become a target for radiation therapy in glioblastoma patients. However, reports studying the effect of irradiation of the SVZ on glioblastoma patient survival show conflicting results. We studied the correlation between incidental SVZ radiation dose and survival in a cohort of isocitrate dehydrogenase-wildtype (IDHwt) glioblastoma patients with inclusion of important survival prognosticators. PATIENTS AND METHODS: In this retrospective analysis, only adult patients with supratentorial IDHwt glioblastoma were included who were treated with temozolomide-based chemoradiotherapy after surgery. The SVZ was contoured on the radiotherapy planning imaging. Cox proportional regression overall survival (OS) analysis was used to study the correlation between SVZ dose and survival. Age, Karnofsky Performance Score, extent of resection and O6-methylguanine-methyl-DNA-transferase gene promoter (MGMTp) methylation were used as covariates in multivariate analysis. RESULTS: In total, 137 patients were included. Median OS was 13.3 months. The MGMTp methylation was present in 40% of cases. Ipsilateral SVZ (iSVZ) mean dose was 44.4 Gy and 27.2 Gy for the contralateral SVZ (cSVZ). Univariate survival analysis showed an inverse relationship between cSVZ mean dose and OS (HR 1.029 (1.003-1.057); p= .032). However, there was no correlation between cSVZ mean dose and OS in multivariate analysis. iSVZ dose did not correlate with survival. CONCLUSION: In this cohort of 137 IDHwt glioblastoma patients, iSVZ did not correlate with OS. Higher cSVZ dose was inversely correlated with OS in univariate survival analysis but lost its significance in multivariate analysis, including MGMTp-methylation. Hence, the correlation between SVZ radiation and glioblastoma patient survival remains unclear. Carefully designed prospective studies are needed to provide unequivocal results on this controversial topic.

Epidemiology and survival of adult-type diffuse glioma in Belgium during the molecular era.

BACKGROUND: Survival data of diffuse adult-type glioma is mostly based on prospective clinical trials or small retrospective cohort studies. Real-world data with large patient cohorts is currently lacking. METHODS: Using the nationwide, population-based Belgian Cancer Registry, all known histological reports of patients diagnosed with an adult-type diffuse glioma in Belgium between 2017 and 2019 were reviewed. The ICD-O-3 morphology codes were matched with the histological diagnosis. The gathered data were transformed into the 2021 World Health Organization classification of CNS tumors using the IDH- and 1p/19q-mutation status. RESULTS: Between 2017 and 2019, 2233 diffuse adult-type gliomas were diagnosed in Belgium. Full molecular status was available in 67.1% of identified cases. The age-standardized incidence rate of diffuse adult-type glioma in Belgium was estimated at 8.55 per 100 000 person-years and 6.72 per 100 000 person-years for grade 4 lesions. Median overall survival time in IDH-wild-type glioblastoma was 9.3 months, significantly shorter compared to grade 4 IDH-mutant astrocytoma (median survival time: 25.9 months). The 3-year survival probability was 86.0% and 75.7% for grades 2 and 3 IDH-mutated astrocytoma. IDH-wild-type astrocytoma has a worse prognosis with a 3-year survival probability of 31.6% for grade 2 and 5.7% for grade 3 lesions. CONCLUSIONS: This registry-based study presents a large cohort of adult-type diffuse glioma with known molecular status and uses real-world survival data. It adds to the current literature which is mainly based on historical landmark trials and smaller retrospective cohort studies.

Partial resection offers an overall survival benefit over biopsy in MGMT-unmethylated IDH-wildtype glioblastoma patients.

Background Isocitrate dehydrogenase (IDH)-wildtype glioblastoma patients with O6-methylguanine-DNA-methyltransferase (MGMT)-unmethylated tumors have the worst outcome of all glioblastoma patients. The overall survival (OS) benefit of partial resection of glioblastoma compared to biopsy only remains controversial specifically in relation to molecular factors. In this report, we analyzed the effect of incomplete resection on OS compared to biopsy only in a cohort of IDH-wildtype glioblastoma patients who were uniformly treated with temozolomide-based chemoradiotherapy (TMZ-CR) after surgery. Material & Methods A retrospective study was conducted including only glioblastoma patients who were treated with TMZ-CR after surgery from two centers. Surgical groups were defined as biopsy only, partial resection (PR) or gross total resection depending on the presence of contrast-enhancing tumor on postoperative imaging. IDH-mutation was determined using next generation sequencing technique and MGMT-methylation was analyzed with semi-quantitative methylation-specific polymerase chain reaction. Next to descriptive statistics, univariate and multivariate survival analyses were performed using Kaplan-Meier estimates and Cox regression models. Results In total, 159 patients were included. 37 patients underwent biopsy only and 73 partial resections. 99 patients (62.3%) harbored unmethylated tumors. Median OS for the whole patient group was 13.4 months. In the subgroup of patients with unmethylated tumors, PR yielded a median OS of 12.2 months vs 7.6 months for biopsy patients (P = 0.003). PR proved an independent beneficial prognostic factor in multivariate Cox regression model, together with age, Karnofsky Performance Score and MGMT-methylation. Conclusion In IDH-wildtype glioblastoma patients with MGMT-unmethylated tumors, treated with chemoradiotherapy after surgery, PR yields a significant OS benefit compared to biopsy.

Postarachnoiditis Anterior Spinal Arachnoid Cyst Formation with Compressive Myelopathy: Report of 2 Cases.

BACKGROUND: Spinal cystic arachnoiditis is a rare complication of a subarachnoid haemorrhage or infectious meningitis. The inflammatory process leads to fibrosis, adhesions, and in severe cases cyst formation. Large arachnoid cysts are an uncommon cause of compressive myelopathy. The majority are located posterior of the spinal cord at the thoracic level. Anterior cyst formation is exceptional, especially at the cervical region. CASE DESCRIPTION: We present 2 cases of progressive myelopathy secondary to anterior arachnoid cyst formation. In a 54-year-old female a large anterior symptomatic thoracic cyst arose 4 years after rupture of a posterior inferior cerebellar artery aneurysm. The other 59-year-old-patient, however, developed an anterior cervical cyst only weeks after a varicella meningoencephalitis. Both female patients were treated with a decompressive laminectomy and wide fenestration of the cysts. Partial recovery was obtained in 1 patient, but there was no improvement in the other case. CONCLUSIONS: Spinal cystic arachnoiditis with anterior cyst formation is an extremely rare complication of subarachnoid haemorrhage and infectious meningitis but can cause severe neurologic deficits. Clinicians should be aware of this rare complication. Due to the risk of irreversible spinal cord injury, rapid surgical intervention is recommended in most cases.

Outcome of Anterior Lumbar Interbody Fusion: A Retrospective Study of Clinical and Radiologic Parameters.

OBJECTIVE: This study critically evaluates the long-term results of standalone anterior lumbar interbody fusion (ALIF), without use of rhBMP-2, as a therapeutic option for symptomatic patients with degenerative disc disease (DDD). Furthermore, this study intends to identify predictive parameters for anterior lumbar interbody fusion outcome. METHODS: A retrospective cohort study with additional telephone interview to obtain missing data was performed. All patients who underwent an L4-L5 or L5-S1 ALIF-procedure, or both, in the period between 2006 and 2011 were identified. The medical files of 123 patients with 154 fusion levels were reviewed. All patients were contacted by telephone to gather supplementary and missing information. Pain and functionality scores (Visual Analogue Scale [VAS] and Oswestry Disability Index [ODI]), radiologic (intervertebral disc height, Modic and Pfirrmann classifications), and different clinical parameters were gathered. RESULTS: The mean age of the population at surgery was 46.2 years. Overall, 59 female and 64 male patients were included in the study. The mean VAS score for back and leg pain improved significantly (P < 0.001) with 5 and 4.4 points respectively at 3-year follow-up. Modic-type I changes are associated with a better improvement in VAS score for back pain (P = 0.026), Pfirrmann-grades IV and V and an intervertebral disc height of less than 5 mm are associated with a better improvement in leg pain (respective P-values: 0.045 and 0.033). Overall, 89% of patients would reconsider the surgical intervention. CONCLUSIONS: The ALIF technique is a durable treatment option for patients with DDD. This study suggests different predictive parameters for treatment outcome.