Adult Supratentorial Ependymoma: The Mayo Clinic Experience

AIMS Solitary fibrous tumours (SFTs) are rare malignant mesenchymal neoplasms within the central nervous system (CNS). Although achieving surgical gross total resection (GTR) is a pivotal prognostic factor, the role and efficacy of postoperative radiotherapy (PORT) remain contentious. This study elucidates our institutional experience, placing particular emphasis on outcomes after PORT administration. METHODS Fourteen patients with CNS SFTs were studied through retrospective review of clinical presentation, radiologic findings, histopathologic characteristics, surgical intervention, adjuvant therapy, and prognosis. Kaplan-Meier survival analysis evaluated overall survival (OS) and recurrence-free survival (RFS) based on the world health organization (WHO) grade, extent of resection (EOR), and application of PORT. RESULTS The cohort included 8 men and 6 women. Magnetic resonance imaging (MRI) revealed slightly hyperintense lesions on T2-weighted images in all patients. All tumours showed positive immunohistochemical staining for signal transducer and activator of transcription 6. WHO grade III tumours had higher Ki-67 indices, stronger CD34 and BCL-2 staining, and more frequent RF positivity compared to WHO grade II tumours. Although grade III tumours exhibited poorer OS than grade II tumours, this was not statistically significant (p = 0.26). RFS was also not significantly different between grades II and III (p = 0.75), though grade III tumours showed earlier recurrences. GTR significantly improved OS compared to subtotal resection (STR) (p = 0.011), with STR patients experiencing a steeper decline in survival. While no significant difference in RFS was noted between GTR and STR (p = 0.45), STR was associated with earlier recurrences. Receiving PORT did not significantly improve OS (p= 0.19) or RFS (p = 0.45) compared to not receiving it. CONCLUSION Achieving complete tumour resection should be prioritised whenever feasible, with adjuvant radiotherapy ad- vised following surgical excision. Additionally, regular and long-term follow-up is imperative to monitor for potential recurrence.

Surgical resection represents the mainstay of treatment in skull base meningiomas (SBMs). Considering the high recurrence rate reported, an adjuvant radiation therapy (RT) treatment should be considered. The aim of this study was to evaluate the progression-free survival (PFS), overall survival (OS), and prognostic factors conditioning outcome. Patients receiving surgical resection for grade I SBMs were included. The extent of resection (EOR) was dichotomized as gross total resection (GTR) and subtotal resection (STR). RT was administered only in patients receiving STR. Clinical outcome was evaluated by brain magnetic resonance imaging (MRI) performed every 6 months for the first year and yearly thereafter. From January 2000 to December 2015, 123 patients were treated. The majority were females (70.7%), with a Karnofsky Performance Score (KPS) ≥80 (95%), and symptoms at diagnosis (91%). GTR was performed in 30% of cases and STR in 70%. RT was performed in 18 (20.9%) patients at diagnosis and in 29 (33.7%) patients at progression. Improvement or stability of neurologic status was obtained in 78.9% of patients. The median follow-up time was 91 months (range: 40-230 months). Local recurrence occurred in 34 (27.6%) patients at a median time of 45 months (range: 6-214 months). The median, 2-, 5-, and 10-year PFS were 193 months, 89.3, 81.8, and 72.5%, respectively. On univariate and multivariate analyses, factors impacting on PFS were EOR, tumor location, neurologic postoperative status, and adjuvant RT in STR. A safe surgical resection followed by RT adjuvant treatment could represent the better choice to obtain local control maintaining neurologic integrity. Our data underlined the value of adjuvant RT in incompletely resected meningiomas.

Purpose: This study is a retrospective analysis to evaluate the impact of fractionated stereotactic radiotherapy (FSRT) on malignant glioma. Material and Methods: Between June 1996 and May 1998, 37 patients with histology-cally proven WHO grade III or IV glioma (17 Anaplastic astrocytoma, 20 Glioblastoma multiforme) were treated at Taipei Medical University hospital with FSRT. External beam radiotherapy (EBRT) delivered a median dose of 46 Gy which is followed by stereotactic radiotherapy. A frameless fractionated stereotactic radiotherapy was used to boost the tumor bed, using daily fraction of 2.0 -3.0 Gy for 5 to 12 fractions. Non-coplanar arcs (4-8 arcs, median 4 arcs) with 1 to 2 isocenters were mostly used. Survival curves were calculated using the Kaplan-Meier method. Prognostic factors and different treatment variables were tested by univariate and multivariate analysis. Results: Overall median survival was 22 months. One year and 2-year survival rate were 60% and 30% respectively. Follow up imaging study showed tumor reduction greater than 50% in 6 patients (16%), reduction less than 50% or unchanged in 14 patients (38%) and progression in 17 of the 37 patients (46%). On analysis of different prognostic factors, patient's age (＜50 years and≧50 years), extent of surgical resection, and tumor volume (＜20 ml) were correlated with survival in univariate analysis (p＜0.05). Tumor volume and extent of surgical resection remained significant in multivariate analysis. The performance status remained stable for all patients during FSRT and only 5 patients (13%) suffered from treatment related acute toxicity with good medication control. Conclusion: Fractionated stereotactic radiotherapy provides a safe and feasible technique in the primary treatment of malignant gliomas. Although the overall survival and 1 year survival is encouraging, we did not observe a significant dose-effect relationship on overall and progression-free survival. Large series study with long term fallow-up is indicated.

The aim of this study was to quantitatively assess the role of intraoperative high-field 3-T MRI (3T-iMRI) in improving the gross-total resection (GTR) rate and the extent of resection (EOR) in endoscopic transsphenoidal surgery (TSS) for pituitary adenomas. Radiological and clinical data from a prospective database were retrospectively analyzed. Volumetric measurements of adenoma volumes pre-, intraoperatively, and 3 months postoperatively were performed in a consecutive series of patients who had undergone endoscopic TSS. The quantitative contribution of 3T-iMRI was measured as a percentage of the additional rate of GTR and of the EOR achieved after 3T-iMRI. The cohort consisted of 50 patients (51 operations) harboring 33 nonfunctioning and 18 functioning pituitary adenomas. Mean adenoma diameter and volume were 21.1 mm (range 5-47 mm) and 5.23 cm(3) (range 0.09-22.14 cm(3)), respectively. According to Knosp's classification, 10 cases were Grade 0; 8, Grade 1; 17, Grade 2; 12, Grade 3; and 4, Grade 4. Gross-total resection was the surgical goal (targeted [t]GTR) in 34 of 51 operations and was initially achieved in 16 (47%) of 34 at 3T-iMRI and in 30 (88%) of 34 cases after further resection. In this subgroup, the EOR increased from 91% at 3T-iMRI to 99% at the 3-month MRI (p < 0.05). In the 17 cases in which subtotal resection (STR) had been planned (tSTR), the EOR increased from 79% to 86% (p < 0.05) and GTR could be achieved in 1 case. Intrasellar remnants were present in 20 of 51 procedures at 3T-iMRI and in only 5 (10%) of 51 procedures after further resection (median volume 0.15 cm(3)). Overall, the use of 3T-iMRI led to further resection in 27 (53%) of 51 procedures and permitted GTR in 15 (56%) of these 27 procedures; thus, the GTR rate in the entire cohort increased from 31% (16 of 51) to 61% (31 of 51) and the EOR increased from 87% to 95% (p < 0.05). The use of high-definition 3T-iMRI allowed precise visualization and quantification of adenoma remnant volume. It helped to increase GTR and EOR rates in both tGTR and tSTR patient groups. Moreover, it helped to achieve low rates of intrasellar remnants. These data support the use of 3T-iMRI to achieve maximal, safe adenoma resection.

Intraoperative Magnetic Resonance Imaging for Low-Grade and High-Grade Gliomas: What Is the Evidence? A Meta-Analysis

Glioneuronal tumors are common neoplasms among the cerebral hemisphere during childhood. They consist of several histological types, of which gangliogliomas (GGs) and dysembryoplastic neuroepithelial tumors (DNTs) are most common and often present with seizures. A great majority of glioneuronal tumors are benign. However, there are conflict reports regarding postoperative tumor recurrence rates and seizure control. The authors analyzed and compared these tumors for their locations and histology and the tumor and seizure control following resection. The authors conducted a retrospective analysis of patients with pediatric glioneuronal tumors in the cerebral hemisphere. All histology reports and neuroimaging are reviewed. Seizure group and non-seizure group were compared with their tumor types and locations. The extent of tumor resections were divided into gross total resection (GTR) and subtotal resection (STR). Postoperative tumor recurrence-free survival (RFS) and seizure-free survival for patients who had the initial surgery done at our institution were calculated using Kaplan-Meier method. There were 90 glioneuronal tumors including 58 GGs, 22 DNTs, 3 papillary glioneuronal tumor, 3 desmoplastic infantile gangliogliomas, 3 anaplastic GGs, and 1 central neurocytoma. Seventy-one patients (seizure group) presented with seizures. The temporal lobe is the most common location, 50% in this series. GTR was attained in 79 patients and STR in 11. All of the patients with GTR had lesionectomy, and only six of them had extended corticectomy or partial lobectomy. Postoperative seizure outcome showed that 64 (90%) of seizure group had Engel's class I, but five patients subsequently developed recurrent seizures. Patients with DNTs had a higher seizure recurrence rate. Tumor RFS was 87% at 5years and 75.5% at 10years. There are no significant difference in tumor recurrences between GGs and DNTs (p = 0.876). Comparison between GRT (67) and STR (9) showed that in spite of the better 5-year tumor RFSs among GRT group (94%) than STR group (66%), the 10-year RFSs showed no significant difference between GRT and STR groups (p = 0.719). Recurrent seizures are often related to recurrent tumor. Lesionectomy alone often provides a high-rate seizure freedom. GGs and DNTs are benign tumor, but recurrences of GGs and DNTs are not uncommon. They may show late recurrences in spite of GTR. These patients need longer follow-up for 10years. Recurrent seizures are often related to a tumor recurrence.

Glioblastoma (GBM) prognosis is influenced by both surgical resection extent and tumor microenvironmental features such as necrosis and extracellular fluid (ECF) accumulation. In this study, we hypothesize that MRI-based radio-pathomic maps (RPMs) of necrotic cell density and ECF volume provide prognostic information beyond standard imaging and vary by surgical resection extent. This study employed MRI-based RPMs to noninvasively characterize tumor microenvironment composition by generating voxel-wise maps of cell density and ECF volume using conventional MRI sequences. These RPMs were developed using a previously validated algorithm trained on spatially aligned histopathological tumor samples, enabling accurate estimation of microenvironment biomarkers outside standard imaging features. We retrospectively analyzed a cohort of 458 GBM patients —210 underwent subtotal resection (STR) and 248 underwent gross total resection (GTR) from the UCSF PDGM dataset. Preoperative T1, T1 post-contrast, ADC, and FLAIR images were processed to create whole tumor RPMs quantifying necrotic cell count and ECF volume. Average cell and ECF volume values were extracted from the RPMs within non-enhancing tumor regions, defined by FLAIR hyperintensity, for each patient. Cox proportional hazards models assessed the prognostic significance of MRI-derived necrosis and ECF metrics on overall survival for each resection type. Higher cell density correlated with poorer survival in the STR (B=2.208, p=0.027) group, whereas increased ECF volumes were associated with improved survival in STR (B=-2.571, p=0.010) and GTR (B=-2.291, p=0.022) patients. These findings demonstrate the effectiveness of integrating histologically informed radio-pathomic imaging biomarkers in the non-enhancing tumor margin for enhanced prognostication for different surgical outcomes, with necrotic presence in the tumor margin driving outcomes across surgical statuses and hypercellular presence specifically impacting subtotal resection patients. Future research could explore the biological mechanisms linking tumor necrosis, extracellular fluid dynamics, and clinical outcomes, as well as the evolution of tissue composition post-treatment.

ObjectiveTo assess the impact of the complete resection of craniopharyngioma (CP) in adults on oncologic and functional outcomes.MethodsWe retrospectively analyzed 82 patients with CP who were surgically treated by the same neurosurgeon at our institution between January 1994 and December 2012.ResultsGross total resection (GTR) was achieved in 71 patients (86.6%), near total resection (NTR) in 7 patients (8.5%), and subtotal resection (STR) in 3 patients (3.7%). The disease-specific overall survival rate was 100% with the exclusion of 2 surgery-related mortalities. The overall recurrence rate was 12.2% (10 of 82 patients), however the recurrence rate according to extent of resection (EOR) was 9.9% (7 of 71 patients) after GTR, 14.3% (1 of 7 patients) after NTR, and 66.7% (2 of 3 patients) after STR. The overall recurrence-free survival (RFS) rates at 5 and 10 years were 87.0% and 76.8%, respectively. Postoperatively, most patients (86.3%) needed hormone replacement for at least 1 hypothalamic-pituitary axis. Vision improved in 56.4% of the patients with preoperative abnormal vision, but deteriorated in 27.4% of patients. Hypothalamic dysfunction developed in 32.9% of patients. There were no significant differences in the risks of pituitary dysfunction, visual deterioration, or hypothalamic dysfunction between the groups with complete vs. incomplete removal. The overall rate of postoperative complications was 22.0%, which did not differ between groups (p=0.053).ConclusionThe complete removal of a CP at first surgery can provide a chance for a cure with acceptable morbidity and mortality risks.

Ependymomas are rare tumors of the central nervous system whose management is controversial. This population-based study of adults and children with ependymoma aims to (1) identify clinical and treatment-related factors that impact survival and (2) determine if postoperative radiotherapy (RT) can improve survival of patients with subtotal resection (STR) to levels similar to patients who had gross total resection (GTR). This retrospective population-based study evaluated 158 patients with ependymoma diagnosed between 1975-2007 in Alberta, Canada. Younger patients (<7 years of age) were more likely to be diagnosed with grade III tumors compared with adults in whom grade I tumors were more common (p=0.003). Adults were more likely to have spinally located tumors compared to young children whose tumors were typically found in the brain. Overall, young children with ependymoma were more likely to die than older children or adults (p=0.001). An equivalent number of patients underwent GTR as compared with STR (48% vs 45%, respectively). Overall, older age, spinal tumor location, lower grade, and GTR were associated with improved progression free survival but only GTR was associated with significant improvement in overall survival. Median survival after STR and RT was 82 months compared with 122 months in patients who had GTR (p=0.0022). This is the first Canadian population-based analysis of patients with ependymoma including adults and children. Extent of resection appears to be the most important factor determining overall survival. Importantly, the addition of RT to patients initially treated with STR does not improve survival to levels similar to patients receiving GTR.

Plasma Matrix Metalloproteinase-9 Predicts Intraoperative Experience and Extent of Resection in Vestibular Schwannoma Surgery.

To assess the evaluation and management of post-surgical residual disease for low-grade intramedullary spinal cord tumours (IMSCT) in childhood. A single-centre retrospective review of low-grade IMSCTs treated between 2000 and 2019. All surgeries were performed with intent of safe maximal resection guided by intra-operative neurophysiological monitoring (IONM). Pre- and post-operative MRIs were reviewed to assess the extent of resection (EOR), recorded as follows: gross total resection (GTR), near total resection (NTR), sub-total resection (STR) and partial resection (PR). Outcome measures were time to recurrence, need for and modality of additional therapy and ambulatory status at last follow-up. Thirty patients underwent surgery for IMSCT (median age 6.9years). EOR was GTR = 8, NTR = 4, STR = 9, PR = 9. All patients were alive at last follow-up (median follow-up 73months [IQR 93months]). Eighteen patients (60%) remained radiologically stable. Twelve patients (40%) developed recurrence during surveillance. Progression free survival was significantly better in cases with GTR + NTR in comparison to either STR or PR (p = 0.039). 10/30 (33%) patients were treated with additional therapy. At last follow-up, 26/30 patients were independently mobile. Survival rates for low-grade IMSCT are excellent. Radical micro-surgical resection, guided by IONM provides effective means of balancing the objectives of maximal safe resection, functional outcome and tumour control. Whilst evidence of 'residual disease' was identified in over 2/3 of immediate post-operative MRI scans, additional treatment was required in only 1/3 of cases. Critical appraisal of post-operative imaging findings is required to better define 'residual disease'. Small volume residual disease (< 5%) does not compromise progression-free survival.

A retrospective study of preoperative and postoperative magnetic resonance imaging (MRI) findings in spinal ependymoma. The goal of the study was to examine MRI features, including the syrinx component volume, after surgical resection of spinal ependymoma, and to relate these features to extent of resection and improvement of postoperative neurological status. Spinal ependymomas have a variety of MRI findings preoperatively, including a hemorrhage cap sign, gadolinium enhancement, and a spinal tumor cyst. However, little is known about these features on postoperative MRI after tumor resection. The subjects were 38 patients treated for spinal cord ependymoma of World Health Organization grade II at our hospital. All had a spinal tumor cyst on preoperative MRI. All cases were followed with MRI for >1 year after surgery, including imaging at postoperative months (POM) 1 and 12. The maximum diameter of the syrinx was measured on mid-sagittal MRI. The extent of tumor resection was categorized as gross total resection (GTR) and subtotal resection (STR). The mean age of the 38 patients (22 male and 16 female individuals) was 50.9 years (range, 21-71 y) at the time of surgery. The mean preoperative duration from disease onset was 14.9 months (range, 2-47 mo). GTR was achieved in 28 patients (74%) and STR in 10 (26%). The mean syrinx sizes preoperatively and at POM 1 and POM 12 were 7.5±2.3, 4.1±1.9, and 2.5±1.8 mm, respectively, with significant differences among the time points (P<0.01). The syrinx size shrunk over time after GTR and STR. The shrinkage rate was significantly higher in GTR cases (P<0.05) and in cases with the improvement of McCormick grade for neurological status after both GTR and STR (P<0.05). These findings suggest that MRI can be used to evaluate the improvement of neurological status after surgery for spinal ependymoma.

Although gross-total resection (GTR) is a preferable treatment for skull base meningiomas, subtotal resection (STR) with or without radiation therapy can be considered as an alternative treatment for patients at considerable surgical risk. The long-term prognosis of such patients might be related to the biological activity of the tumor. This study examined predictors of progression-free survival (PFS) and sought to determine the optimal treatment strategies, focusing on the pathobiological findings of skull base meningiomas. This study included 281 patients with skull base meningiomas (mean follow-up period 88.4 months). Risk factors for tumor progression were examined using a multivariate analysis. The PFS and overall survival (OS) rates were evaluated using the Kaplan-Meier method. The functional outcomes of the patients were measured using the Karnofsky Performance Scale (KPS). The 10-year PFS and OS rates were 66.4% and 97.4%, respectively. Overall, 83.3% of patients achieved a favorable outcome, that is, an improved or unchanged KPS score. The extent of resection, additional radiotherapy, histological grade, MIB-1 index, and p53-positive rate were significantly associated with PFS. The PFS of patients undergoing STR without radiation therapy was significantly shorter than that of either those undergoing STR with radiation therapy or GTR, while no statistical difference was observed between the latter 2 groups. Among the patients undergoing STR with pathobiological risk factors (histological grade, MIB-1 index, and p53-positive rate), the PFS of the patients who received radiation therapy was better than that of those who did not receive radiation therapy. Among the patients undergoing STR without such risk factors, the PFS was not significantly different between patients who received radiation therapy and those who did not. For patients with skull base meningiomas, a GTR is desirable and additional radiation therapy after STR may contribute to a longer PFS. Additional radiation therapy should be recommended, especially for patients with pathobiological risk factors, but not necessarily for those without such risks.

Giant pituitary adenoma is considered a challenging pathology for surgery owing to its complications and low resection rate. In this study, the authors present their experience of using the endoscopic endonasal approach to treat patients with giant pituitary adenoma, and they aimed to develop a classification system for prediction of extent of resection. The institutional medical records of patients diagnosed with giant pituitary adenoma who underwent endoscopic endonasal transsphenoidal surgery between August 1997 and December 2019 were retrospectively reviewed. Surgical and clinical outcomes were evaluated in detail. The effects of tumor characteristics on extent of resection were analyzed. The findings were used to develop two classification systems that could preoperatively predict extent of resection. Morphological score was based on tumor characteristics, and landmark-based classification was defined according to surgical zones based on neurovascular landmarks. The effects of change in surgical strategy, which aimed to maximize tumor resection and capsule dissection, on rates of resection and complications were evaluated before and after 2017. This study included 205 patients, with a mean patient age of 46.95 years and mean preoperative tumor diameter of 46.56 mm. Gross-total resection (GTR) was achieved in 35.12% of patients, near-total resection (NTR) in 39.51%, and subtotal resection (STR) in 25.36%. Extent of resection differed significantly between the grades and zones of the classification systems (p < 0.001 for both). Among patients with grade 3 tumor, 75.75% of patients achieved STR, 21.21% achieved NTR, and 3.03% achieved GTR. Among patients with zone 3 tumor, 65.75% achieved STR, 32.87% achieved NTR, and 1.36% achieved GTR. Both grade 3 and zone 3 indicated limited extent of resection. The mean (range) follow-up duration was 50.16 (9-247) months. Postoperative recovery of at least one hormone axis was seen in 15.24% of patients with pituitary deficiency, and development of new hormonal deficiency was observed in 22.43% of patients. Complications included permanent diabetes insipidus (7.80%), cerebrospinal fluid leakage (3.90%), postoperative apoplexy (3.90%), meningitis (3.41%), and epistaxis (3.41%). The surgical mortality rate was 1.46%. Among 85 patients treated before 2017, 27.05% of patients achieved GTR, 37.64% achieved NTR, and 35.29% achieved STR; among 120 patients treated after 2017, 40.83% achieved GTR, 40.83% achieved NTR, and 18.33% achieved STR. Seven patients in the pre-2017 cohort had postoperative apoplexy versus only 1 patient in the post-2017 cohort. There were no statistically significant differences between the two periods in terms of the incidence rates of other complications. Capsule dissection and GTR are valuable for preventing serious complications and reducing recurrence of giant adenoma. Treatment of giant pituitary adenoma may be better managed with the help of a classification system that provides information about extent of resection that can be achieved with an endoscopic approach.

Kaur et al1 have produced a timely systematic review on the role of adjuvant radiotherapy for atypical meningioma (AM) and malignant meningioma. Their review highlights the paucity of good quality prospective studies and the urgent need for prospective clinical trials for AM. Kaur et al1 identify extent of resection (EOR) as an important prognostic factor but fail to comment on how this was defined. In 1957 Simpson2 described a classification system that is still used today. The Simpson classification predates CT and MRI and is based upon the neurosurgeon′s assessment. Recently, several authors have questioned the use of Simpson grading in modern neurosurgery as a prognostic factor for risk of tumor recurrence,3 instead proposing a change that defines EOR as either gross total resection (GTR) or subtotal resection (STR). In a recent review paper, GTR was described as Simpson 1–3, that is, no residual solid tumor, while STR equated to Simpson 4–5.4 These definitions have been endorsed by both the European Organisation for Research and Treatment of Cancer (EORTC) and the Radiation Therapy Oncology Group (RTOG), and most prospective clinical trials for meningioma adopt this definition. The latest World Health Organization classification5 has led to increased reporting of AM,6–8 and there continues to be a marked institutional variation in patient management, particularly the use of early adjuvant radiotherapy.9,10 Despite meningiomas being considered relatively radioresistant, radiotherapy remains the only available adjuvant therapy for these tumors in routine clinical practice. The role of early adjuvant radiotherapy for patients with AM who undergo a GTR, however, remains to be defined,1 leading to a lack of class I evidence.11 Of these retrospective studies, patient numbers in the radiotherapy and observation arms are frequently unequal, and the relatively short median time to recurrence emphasizes the nonbenign nature of these tumors. Moreover, the treatment decision (ie, adjuvant radiotherapy vs no adjuvant radiotherapy) after surgery is likely to depend on the patient′s pretreatment characteristics. As in any retrospective analysis, there are differences in known and unknown prognostic factors, which may be associated with patient outcome. As such, the assessment of the radiotherapy effect in these studies suffers from bias caused by confounding by indication.12 One further major limitation of all these studies is the lack of data on health-related quality of life. Kaur et al add to the repeated calls for a definitive clinical trial.1,4,9,11,13 We are pleased to report on a collaborative trial that has been developed between the UK and EORTC. The ROAM/EORTC 1308 trial (ISRCTN71502099) (Radiation vs Observation following surgical resection of Atypical Meningioma) is a multicenter, phase III, randomized controlled trial that will answer the question “In patients who have undergone GTR of AM, does early adjuvant radiotherapy reduce recurrence compared with active monitoring?” Patients will be randomized 1 : 1 between early adjuvant fractionated external beam radiotherapy and active surveillance with serial MRI scans (Fig. 1). The primary outcome is time to MRI evidence of local recurrence (disease-free survival), and secondary outcomes include time to second line treatment, time to death, toxicity of treatment, quality of life, neurocognitive function, and health economic analysis. Across Europe, approximately 20 centers have expressed interest in participating, of which 10 are in the UK. The study is powered to detect an absolute reduction in recurrence rate from 40% (control arm) to 20% (radiotherapy arm) and will recruit 172 patients in total. Due to the rarity of AM, it is anticipated that this trial will run for a total of 10 years. Since the patient journey starts with the resection, neurosurgeons will be critical to the success of this trial. An appreciation of genuine clinical equipoise and lack of class I evidence to support current variations in practice are paramount. Trials of intervention versus monitoring can pose a recruitment challenge, since clinicians and patients often exhibit bias.14,15 In the ROAM/EORTC 1308 trial, strategies will be employed that ensure clinicians present the trial in an unbiased way to patients in order to maximize recruitment.16 An award of £1.36 million has been made to M.D.J. by the National Institute for Health Research Health Technology Programme to fund this trial, with additional funding from Europe (to D.C.W.). The trial is scheduled to open in November 2014. Fig. 1. ROAM/EORTC 1308 study design.