The ROAM/EORTC-1308 trial: Radiation versus Observation following surgical resection of Atypical Meningioma: study protocol for a randomised controlled trial

Abstract

BackgroundAtypical 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.Methods/DesignA 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.DiscussionROAM/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.Trial registrationISRCTN71502099 on 19 May 2014.

Gross total resection and adjuvant radiotherapy most significant predictors of improved survival in patients with atypical meningioma

“…26 This will be tested in the future with NRG Oncology protocol BN-003 and the ongoing Radiation versus Observation following surgical resection of Atypical Meningioma (ROAM)/European Organization for Research and Treatment of Cancer (EORTC)-1308 trial, for which, based on the results of the current study, we would support patient enrollment for the evaluation of disease-free-survival. 27 Although studies to date have demonstrated improvement in disease control with RT, the results of the current study (which we believe to have enough patients and follow-up) actually suggested that this improved control is likely to lead to improved survival in the future. On multivariate analysis, the current study data also demonstrated poorer survival in African American patients.…”

“…The preliminary results (in abstract form) of the phase 2 NRG/Radiation Therapy Oncology Group (RTOG) 0539 study found that a combination of surgery/RT led to significantly improved progression‐free survival in a group of patients treated for recurrent grade 1 lesions and completely resected atypical lesions . This will be tested in the future with NRG Oncology protocol BN‐003 and the ongoing Radiation versus Observation following surgical resection of Atypical Meningioma (ROAM)/European Organization for Research and Treatment of Cancer (EORTC)‐1308 trial, for which, based on the results of the current study, we would support patient enrollment for the evaluation of disease‐free‐survival . Although studies to date have demonstrated improvement in disease control with RT, the results of the current study (which we believe to have enough patients and follow‐up) actually suggested that this improved control is likely to lead to improved survival in the future.…”

“Homogenous subgroups of atypical meningiomas defined using oncogenic signatures: basis for a new grading system?”

“…These homogenous subgroups may help predict clinical course, thus allowing for customized follow-up planning to manage resource intense investigations such serial imaging while optimizing patient care. Our results could also help guide recruitment protocols for future and ongoing clinical trials, which are currently limited by the uncertainty of clinical outcomes in atypical meningiomas 24 . The approach in this study lend to the utility of complex molecular signatures in augmenting histological diagnosis and resolving other heterogeneous and challenging diseases.…”

‘Meningiomics’—an integration of data on the patient, tumour, extent of resection and molecular pathology to optimise the management and follow-up for meningiomas

“…Thirdly, the use of a competing risk analysis is appropriate in meningioma when there is a high risk that the event of interest (meningioma recurrence or meningioma-related death) will not be observed due to the high prevalence of over events, that is, death due to other causes. Indeed, this is the rationale behind current phase III atypical meningioma trials excluding patients with co-existing solid cancers [5] since the event of interest is recurrence.…”