Atypical meningiomas are an intermediate grade brain tumour with a recurrence rate of 39–58 %. It is not known whether early adjuvant radiotherapy reduces the risk of tumour recurrence and whether the potential side-effects are justified. An alternative management strategy is to perform active monitoring with magnetic resonance imaging (MRI) and to treat at recurrence. There are no randomised controlled trials comparing these two approaches. A total of 190 patients will be recruited from neurosurgical/neuro-oncology centres across the United Kingdom, Ireland and mainland Europe. Adult patients undergoing gross total resection of intracranial atypical meningioma are eligible. Patients with multiple meningioma, optic nerve sheath meningioma, previous intracranial tumour, previous cranial radiotherapy and neurofibromatosis will be excluded. Informed consent will be obtained from patients. This is a two-stage trial (both stages will run in parallel): Stage 1 (qualitative study) is designed to maximise patient and clinician acceptability, thereby optimising recruitment and retention. Patients wishing to continue will proceed to randomisation. Stage 2 (randomisation) patients will be randomised to receive either early adjuvant radiotherapy for 6 weeks (60 Gy in 30 fractions) or active monitoring. The primary outcome measure is time to MRI evidence of tumour recurrence (progression-free survival (PFS)). Secondary outcome measures include assessing the toxicity of the radiotherapy, the quality of life, neurocognitive function, time to second line treatment, time to death (overall survival (OS)) and incremental cost per quality-adjusted life year (QALY) gained. ROAM/EORTC-1308 is the first multi-centre randomised controlled trial designed to determine whether early adjuvant radiotherapy reduces the risk of tumour recurrence following complete surgical resection of atypical meningioma. The results of this study will be used to inform current neurosurgery and neuro-oncology practice worldwide. ISRCTN71502099 on 19 May 2014.
Surgery has long been established as the first-line treatment for the majority of symptomatic and enlarging meningiomas, and evidence for its success is derived from retrospective case series. Despite surgical resection, a subset of meningiomas display aggressive behavior with early recurrences that are difficult to treat. The decision to radically resect meningiomas and involved structures is balanced against the risk for neurological injury in patients. Radiation therapy has largely been used as a complementary and safe therapeutic strategy in meningiomas with evidence primarily stemming from retrospective, single-institution reports. Two of the first cooperative group studies (RTOG 0539 and EORTC 22042) evaluating the outcomes of adjuvant radiation therapy in higher-risk meningiomas have shown promising preliminary results. Historically, systemic therapy has resulted in disappointing results in meningiomas. However, several clinical trials are under way evaluating the efficacy of chemotherapies, such as trabectedin, and novel molecular agents targeting Smoothened, AKT1, and focal adhesion kinase in patients with recurrent meningiomas.
Background Incidental discovery accounts for 30% of newly-diagnosed intracranial meningiomas. There is no consensus on their optimal management. This review aimed to evaluate the outcomes of different management strategies for these tumors. Methods Using established systematic review methods, six databases were scanned up to September 2017. Pooled event proportions were estimated using a random effects model. Meta-regression of prognostic factors was performed using individual patient data. Results Twenty studies (2130 patients) were included. Initial management strategies at diagnosis were: surgery (27.3%), stereotactic radiosurgery (22.0%) and active monitoring (50.7%) with a weighted mean follow-up of 49.5 months (SD = 29.3). The definition of meningioma growth and monitoring regimens varied widely impeding relevant meta-analysis. The pooled risk of symptom development in patients actively monitored was 8.1% (95% CI 2.7–16.1). Associated factors were peritumoral edema (OR 8.72 [95% CI 0.35–14.90]) and meningioma diameter ≥ 3 cm (OR 34.90 [95% CI 5.17–160.40]). The pooled proportion of intervention after a duration of active monitoring was 24.8% (95% CI 7.5–48.0). Weighted mean time-to-intervention was 24.8 months (SD = 18.2). The pooled risks of morbidity following surgery and radiosurgery, accounting for cross-over, were 11.8% (95% CI 3.7–23.5) and 32.0% (95% CI 10.6–70.5) respectively. The pooled proportion of operated meningioma being WHO grade I was 94.0% (95% CI 88.2–97.9). Conclusion The management of incidental meningioma varies widely. Most patients who clinically or radiologically progressed did so within 5 years of diagnosis. Intervention at diagnosis may lead to unnecessary overtreatment. Prospective data is needed to develop a risk calculator to better inform management strategies.
Oligodendroglial neoplasms with the -1p/-19q genotype are more indolent with longer survival and increased therapeutic responsiveness than those with intact 1p/19q, but the biological basis for these clinical differences is unclear. Recent research suggests that oligodendrogliomas with and without the -1p/-19q genotype may be distinguished by their magnetic resonance imaging (MRI) appearance, suggesting possible differences in growth characteristics. This study examined the relationship between genotype and histological growth patterns of oligodendroglial neoplasms in association with MR imaging characteristics. Tumour imaging features assessed on MRI included sharp-versus-indistinct border, smooth-versus-irregular contour, homogeneous-versus-heterogeneous signal, contrast enhancement and paramagnetic susceptibility effect. Growth patterns (solid : mixed : infiltrative), tumour-margin transitions in cellularity and calcification were determined histopathologically. Allelic imbalance in chromosomes 1p36 and 19q13 was determined. Thirty-three oligodendrogliomas (25 with 1p/19q loss) and 53 oligoastrocytomas (18 with 1p/19q loss) were investigated. Solid, mixed or infiltrative growth patterns were seen in grade II and grade III tumours with or without 1p/19q loss, but infiltrative growth was more common in tumours with intact 1p/19q (chi2: P = 0.029). Grade III tumours were more likely to have a solid growth pattern (chi2: P = 0.046) associated with contrast enhancement (chi2: P = 0.011). Transition in cellularity at the radiological margin did not differ according to genotype. All cases with T1 or T2 signal homogeneity had intact 1p/19q. Tumours with sharp/smooth borders were more likely to have intact 1p/19q than those with indistinct/irregular borders (chi2: P < 0.001), but this was not related to histological growth characteristics. This study identified a group of oligodendroglial tumours with intact 1p/19q displaying distinctive MR imaging features that were unrelated to the histopathology characteristics.
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.