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This case shows the feasibility of targeted muscle reinnervation (TMR) in a patient with a traumatic neuroma of the medial antebrachial cutaneous nerve (MABCN). TMR was performed by connecting the proximal stump of the MABCN to the branch innervating the accessory epitrochleoanconeus muscle. Postoperatively, the patient reported significantly less pain., Competing Interests: None of the authors declare a conflict of interest., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)

Purpose: Previous evidence suggests that glioma re-resection can be effective in improving clinical outcomes. Furthermore, the use of mapping techniques during surgery has proven beneficial for newly diagnosed glioma patients. However, the effects of these mapping techniques during re-resection are not clear. This systematic review aimed to assess the evidence of using these techniques for recurrent glioma patients., Methods: A systematic search was performed to identify relevant studies. Articles were eligible if they included adult patients with recurrent gliomas (WHO grade 2-4) who underwent re-resection. Study characteristics, application of mapping, and surgical outcome data on survival, patient functioning, and complications were extracted., Results: The literature strategy identified 6372 articles, of which 125 were screened for eligibility. After full-text evaluation, 58 articles were included in this review, comprising 5311 patients with re-resection for glioma. Of these articles, 17% (10/58) reported the use of awake or asleep intraoperative mapping techniques during re-resection. Mapping was applied in 5% (280/5311) of all patients, and awake craniotomy was used in 3% (142/5311) of the patients., Conclusion: Mapping techniques can be used during re-resection, with some evidence that it is useful to improve clinical outcomes. However, there is a lack of high-quality support in the literature for using these techniques. The low number of studies reporting mapping techniques may, next to publication bias, reflect limited application in the recurrent setting. We advocate for future studies to determine their utility in reducing morbidity and increasing extent of resection, similar to their benefits in the primary setting., Competing Interests: Declarations Conflicts of interest The authors have not disclosed any competing interests., (© 2024. The Author(s).)

For glioblastoma patients, the efficacy-targeted therapy is limited to date. Most of the molecular therapies previously studied are lacking efficacy in this population. More trials are needed to study the actual actionability of biomarkers in (recurrent) glioblastoma. This study aimed to assess the current clinical trial landscape to assess the role of molecular biomarkers in trials on recurrent glioblastoma treatment. The database ClinicalTrials.gov was used to identify not yet completed clinical trials on recurrent glioblastoma in adults. Recruiting studies were assessed to investigate the role of molecular criteria, which were retrieved as detailed as possible. Primary outcome was molecular criteria used as selection criteria for study participation. Next to this, details on moment and method of testing, and targets and drugs studied, were collected. In 76% (181/237) of the included studies, molecular criteria were not included in the study design. Of the remaining 56 studies, at least one specific genomic alteration as selection criterium for study participation was required in 33 (59%) studies. Alterations in EGFR, CDKN2A/B or C, CDK4/6, and RB were most frequently investigated, as were the corresponding drugs abemaciclib and ribociclib. Of the immunotherapies, CAR-T therapies were the most frequently studied therapies. Previously, genomics studies have revealed the presence of potentially actionable alterations in glioblastoma. Our study shows that the potential efficacy of targeted treatment is currently not translated into genome-driven trials in patients with recurrent glioblastoma. An intensification of genome-driven trials might help in providing evidence for (in)efficacy of targeted treatments., (© 2024. The Author(s).)

Increased use of whole genome sequencing (WGS) in neuro-oncology for diagnostics and research purposes necessitates a renewed conversation about informed consent procedures and governance structures for sharing personal health data. There is currently no consensus on how to obtain informed consent for WGS in this population. In this narrative review, we analyze the formats and contents of frameworks suggested in literature for WGS in oncology and assess their benefits and limitations. We discuss applicability, specific challenges, and legal context for patients with (recurrent) glioblastoma. This population is characterized by the rarity of the disease, extremely limited prognosis, and the correlation of the stage of the disease with cognitive abilities. Since this has implications for the informed consent procedure for WGS, we suggest that the content of informed consent should be tailor-made for (recurrent) glioblastoma patients., (© 2024. The Author(s).)

Purpose: The gold standard for diagnostics in primary central nervous system lymphoma (PCNSL) is histopathological diagnosis after stereotactic biopsy. Yet, PCNSL has a multidisciplinary diagnostic work up, which associated with diagnostic delay and could result in treatment delay. This article offers recommendations to neurosurgeons involved in clinical decision-making regarding (novel) diagnostics and care for patients with PCNSL with the aim to improve uniformity and timeliness of the diagnostic process for patients with PCNSL., Methods: We present a mini review to discuss the role of stereotactic biopsy in the context of novel developments in diagnostics for PCNSL, as well as the role for cytoreductive surgery., Results: Cerebrospinal fluid-based diagnostics are supplementary and cannot replace stereotactic biopsy-based diagnostics., Conclusion: Histopathological diagnosis after stereotactic biopsy of the brain remains the gold standard for diagnosis. Additional diagnostics should not be a cause of diagnostic delay. There is currently no sufficient evidence supporting cytoreductive surgery in PCNSL, with recent studies showing contradictive data and suboptimal study designs., (© 2024. The Author(s).)

Purpose: Next generation sequencing (NGS) is an important tool used in clinical practice to obtain the required molecular information for accurate diagnostics of high-grade adult-type diffuse glioma (HGG). Since individual centers use either in-house produced or standardized panels, interlaboratory variation could play a role in the practice of HGG diagnosis and treatment. This study aimed to investigate the current practice in NGS application for both primary and recurrent HGG., Methods: This nationwide Dutch survey used the expertise of (neuro)pathologists and clinical scientists in molecular pathology (CSMPs) by sending online questionnaires on clinical and technical aspects. Primary outcome was an overview of panel composition in the different centers for diagnostic practice of HGG. Secondary outcomes included practice for recurrent HGG and future perspectives., Results: Out of twelve neuro-oncology centers, the survey was filled out by eleven (neuro)pathologists and seven CSMPs. The composition of the diagnostic NGS panels differed in each center with numbers of genes ranging from 12 to 523. Differences are more pronounced when tests are performed to find therapeutic targets in the case of recurrent disease: about half of the centers test for gene fusions (60%) and tumor mutational burden (40%)., Conclusion: Current notable interlaboratory variations as illustrated in this study should be reduced in order to refine diagnostics and improve precision oncology. In-house developed tests, standardized panels and routine application of broad gene panels all have their own advantages and disadvantages. Future research would be of interest to study the clinical impact of variation in diagnostic approaches., (© 2024. The Author(s).)

Background: IDH1/2 wildtype (IDHwt) glioma WHO grade 2 and 3 patients with pTERT mutation and/or EGFR amplification and/or + 7/-10 chromosome gain/loss have a similar overall survival time as IDHwt glioblastoma patients, and are both considered glioblastoma IDHwt according to the WHO 2021 classification. However, differences in seizure onset have been observed. This study aimed to compare the course of epilepsy in the 2 glioblastoma subtypes., Methods: We analyzed epilepsy data of an existing cohort including IDHwt histologically lower-grade glioma WHO grade 2 and 3 with molecular glioblastoma-like profile (IDHwt hLGG) and IDHwt glioblastoma patients. Primary outcome was the incidence proportion of epilepsy during the disease course. Secondary outcomes included, among others, onset of epilepsy, number of seizure days, and antiepileptic drug (AED) polytherapy., Results: Out of 254 patients, 78% (50/64) IDHwt hLGG and 68% (129/190) IDHwt glioblastoma patients developed epilepsy during the disease (P = .121). Epilepsy onset before histopathological diagnosis occurred more frequently in IDHwt hLGG compared to IDHwt glioblastoma patients (90% vs 60%, P < .001), with a significantly longer median time to diagnosis (3.5 vs 1.3 months, P < .001). Median total seizure days was also longer for IDHwt hLGG patients (7.0 vs 3.0, P = .005), and they received more often AED polytherapy (32% vs 17%, P = .028)., Conclusions: Although the incidence proportion of epilepsy during the entire disease course is similar, IDHwt hLGG patients show a significantly higher incidence of epilepsy before diagnosis and a significantly longer median time between first seizure and diagnosis compared to IDHwt glioblastoma patients, indicating a distinct clinical course., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Despite current best treatment options, a glioblastoma almost inevitably recurs after primary treatment. However, in the absence of clear evidence, current guidelines on recurrent glioblastoma are not well-defined. Re-resection is one of the possible treatment modalities, though it can be challenging to identify those patients who will benefit. Therefore, treatment decisions are made based on multidisciplinary discussions. This study aimed to investigate the current practice variation between neuro-oncology specialists., Methods: In this nationwide study among Dutch neuro-oncology specialists, we surveyed possible practice variation. Via an online survey, 4 anonymized recurrent glioblastoma cases were presented to neurosurgeons, neuro-oncologists, medical oncologists, and radiation oncologists in The Netherlands using a standardized questionnaire on whether and why they would recommend a re-resection or not. The results were used to provide a qualitative analysis of the current practice in The Netherlands., Results: The survey was filled out by 56 respondents, of which 15 (27%) were neurosurgeons, 26 (46%) neuro-oncologists, 2 (4%) medical oncologists, and 13 (23%) radiation oncologists. In 2 of the 4 cases, there appeared to be clinical equipoise. Overall, neurosurgeons tended to recommend re-resection more frequently compared to the other specialists. Neurosurgeons and radiation oncologists showed opposite recommendations in 2 cases., Conclusions: This study showed that re-resection of recurrent glioblastoma is subject to practice variation both between and within neuro-oncology specialties. In the absence of unambiguous guidelines, we observed a relationship between preferred practice and specialty. Reduction of this practice variation is important; to achieve this, adequate prospective studies are essential., Competing Interests: None of the authors declare a conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Glioblastoma (GBM), the most common glial primary brain tumour, is without exception lethal. Every year approximately 600 patients are diagnosed with this heterogeneous disease in The Netherlands. Despite neurosurgery, chemo -and radiation therapy, these tumours inevitably recur. Currently, there is no gold standard at time of recurrence and treatment options are limited. Unfortunately, the results of dedicated trials with new drugs have been very disappointing. The goal of the project is to obtain the evidence for changing standard of care (SOC) procedures to include whole genome sequencing (WGS) and consequently adapt care guidelines for this specific patient group with very poor prognosis by offering optimal and timely benefit from novel therapies, even in the absence of traditional registration trials for this small volume cancer indication., Methods: The GLOW study is a prospective diagnostic cohort study executed through collaboration of the Hartwig Medical Foundation (Hartwig, a non-profit organisation) and twelve Dutch centers that perform neurosurgery and/or treat GBM patients. A total of 200 patients with a first recurrence of a glioblastoma will be included. Dual primary endpoint is the percentage of patients who receive targeted therapy based on the WGS report and overall survival. Secondary endpoints include WGS report success rate and number of targeted treatments available based on WGS reports and number of patients starting a treatment in presence of an actionable variant. At recurrence, study participants will undergo SOC neurosurgical resection. Tumour material will then, together with a blood sample, be sent to Hartwig where it will be analysed by WGS. A diagnostic report with therapy guidance, including potential matching off-label drugs and available clinical trials will then be sent back to the treating physician for discussing of the results in molecular tumour boards and targeted treatment decision making., Discussion: The GLOW study aims to provide the scientific evidence for changing the SOC diagnostics for patients with a recurrent glioblastoma by investigating complete genome diagnostics to maximize treatment options for this patient group., Trial Registration: ClinicalTrials.gov Identifier: NCT05186064., (© 2022. The Author(s).)

Background: Traumatic neuromata often recur after resection. Recently, targeted muscle reinnervation (TMR) has been shown to be a promising alternative for the treatment of traumatic neuroma, also in nonamputees. This case shows that TMR can also be applied for this indication in recurrent traumatic neuroma., Observations: A 55-year-old patient with a history of cerebral palsy presented with a painful swelling in his right knee, 40 years after multiple Achilles tendon surgeries for contractures. On imaging, the lesion was suspect for a traumatic neuroma of the posterior sural nerve. After two failed resections, TMR was performed by connecting the proximal end of the sural nerve to the motor branch of the lateral gastrocnemius muscle. During outpatient visits at 3, 6, and 12 months, the patient reported significantly less pain compared to before the TMR. He had no weakness of plantar flexion. Postoperative imaging, however, showed atrophy of the lateral gastrocnemius muscle., Lessons: This case shows that TMR can be a successful strategy to treat recurrent traumatic neuroma after previous failed transection of single neuromata in nonamputee cases. In the authors' patient, TMR did not result in motor deficit, but more research is needed to investigate this consequence of TMR for this indication.

Purpose: Optimal treatment with antiepileptic drugs (AEDs) is an important part of care for brain tumor patients with epileptic seizures. Lamotrigine and lacosamide are both examples of frequently used non-enzyme inducing AEDs with limited to no drug-drug interactions, reducing the risk of unfavorable side effects. This study aimed to compare the effectiveness of lamotrigine versus lacosamide., Methods: In this multicenter study we retrospectively analyzed data of patients with diffuse grade 2-4 glioma with epileptic seizures. All patients received either lamotrigine or lacosamide during the course of their disease after treatment failure of first-line monotherapy with levetiracetam or valproic acid. Primary outcome was the cumulative incidence of treatment failure, from initiation of lamotrigine or lacosamide, with death as competing event, for which a competing risk model was used. Secondary outcomes were uncontrolled seizures after AED initiation and level of toxicity., Results: We included a total of 139 patients of whom 61 (44%) used lamotrigine and 78 (56%) used lacosamide. At 12 months, there was no statistically significant difference in the cumulative incidence of treatment failure for any reason between lamotrigine and lacosamide: 38% (95%CI 26-51%) versus 30% (95%CI 20-41%), respectively. The adjusted hazard ratio for treatment failure of lacosamide compared to lamotrigine was 0.84 (95%CI 0.46-1.56). The cumulative incidences of treatment failure due to uncontrolled seizures (18% versus 11%) and due to adverse events (17% versus 19%) did not differ significantly between lamotrigine and lacosamide., Conclusion: Lamotrigine and lacosamide show similar effectiveness in diffuse glioma patients with epilepsy., (© 2021. The Author(s).)

Patients with melanoma brain metastases (MBM) still have a very poor prognosis. Several treatment modalities have been investigated in an attempt to improve the management of MBM. This review aimed to evaluate the impact of current treatments for MBM on patient- and tumor-related outcomes, and to provide treatment recommendations for this patient population. A literature search in the databases PubMed, Embase, Web of Science and Cochrane was conducted up to January 8, 2019. Original articles published since 2010 describing patient- and tumor-related outcomes of adult MBM patients treated with clearly defined systemic therapy were included. Information on basic trial demographics, treatment under investigation and outcomes (overall and progression-free survival, local and distant control and toxicity) were extracted. We identified 96 eligible articles, comprising 95 studies. A large variety of treatment options for MBM were investigated, either used alone or as combined modality therapy. Combined modality therapy was investigated in 71% of the studies and resulted in increased survival and better distant/local control than monotherapy, especially with targeted therapy or immunotherapy. However, neurotoxic side-effects also occurred more frequently. Timing appeared to be an important determinant, with the best results when radiotherapy was given before or during systemic therapy. Improved tumor control and prolonged survival can be achieved by combining radiotherapy with immunotherapy or targeted therapy. However, more randomized controlled trials or prospective studies are warranted to generate proper evidence that can be used to change the standard of care for patients with MBM., (© 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)