Neoplasms

Nervous System Diseases

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Rare Diseases

Meningioma

Neoplasms, Nerve Tissue

Neoplasms by Histologic Type

Neoplasms, Vascular Tissue

Meningeal Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Patients undergo observation after gross total resection.

Patients undergo radiation therapy 5 days a week over 6.5-7 weeks for a total of 33 fractions after gross total resection.

Clinical Observation

Radiation Therapy

C. Leland Rogers, MD

Site Public Contact

Igor J. Barani

Baldassarre Stea

Michael R. Girvigian

Christopher U. Jones

Samantha A. Seaward

Eric L. Chang

Xiao-Tang Kong

Alexis M. Demopoulos

Nicholas A. Blondin

Eric A. Mellon

Michael R. Olson

Sherif Makar

Hsiang-Hsuan M. Yu

Bree R. Eaton

Adam W. Nowlan

Richard Y. Lee

Sean Sachdev

Ken Tatebe

Matthew Koshy

Bruce E. Brockstein

Vinai Gondi

Anupama Chundury

Gary V. Burton

Matthew D. Cheney

John E. Mignano

Eleanor M. Walker

Samir Narayan

Bret E. Friday

Yan Ji

Gregory B. Biedermann

Jiayi Huang

This randomized phase III trial studies how well radiation therapy works compared with observation in treating patients with newly diagnosed grade II meningioma that has been completely removed by surgery. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors.

PRIMARY OBJECTIVES:

I. To determine, in terms of progression-free survival (PFS), the extent of clinical benefit of the addition of adjuvant radiotherapy (RT) to gross total resection (GTR) for patients with newly diagnosed World Health Organization (WHO) grade II meningioma.

SECONDARY OBJECTIVES:

I. Overall survival (OS). II. Disease-specific survival (DSS). III. Toxicity (grade 3+, exclusive of expected alopecia). IV. Neurocognitive function (NCF). V. Outcomes and patient reported outcomes (PRO) measurements. VI. Adherence to protocol-specific target and normal tissue parameters. VII. Concordance measurements of central versus parent-institution pathology. VIII. Tissue microarray construction, and assessment of pHH3 mitotic index and molecular correlates to OS.

OUTLINE: Patients are randomized to 1 of 2 arms after undergoing gross total resection.

ARM I: Patients undergo observation.

ARM II: Patients undergo radiation therapy 5 days a week over 6.5-7 weeks for a total of 33 fractions (59.4 Gy in 33 daily fractions of 1.8 Gy each).

After completion of study treatment, patients are followed up at 3, 6, and 12 months, every 6 months for year 2 and 3, then yearly for 10 years.

Observation or Radiation Therapy in Treating Patients With Newly Diagnosed Grade II Meningioma That Has Been Completely Removed by Surgery

Phase III Trial of Observation Versus Irradiation for a Gross Totally Resected Grade II Meningioma

Kaplan-Meier method will be used to calculate the PFS rates for each of the two arms (Kaplan 1958). Hazard ratio (HR) on the treatment effect will be calculated using the Cox proportional hazard model (Cox 1972). A one-sided log-rank test will be used to test the difference in PFS between the two arms (Peto 1972).

Kaplan-Meier method will be used to calculate the OS rates for each of the two arms (Kaplan 1958). Hazard ratio (HR) on the treatment effect will be calculated using the Cox proportional hazard model (Cox 1972). A one-sided log-rank test will be used to test the difference in OS between the two arms (Peto 1972). Cox proportional hazard model will be used to determine the adjusted treatment effect on OS, with patient pretreatment characteristics as covariates.

Will be calculated based on the Kaplan-Meier curve.

Will be calculated using the cumulative incidence function for each arm. The HR for the treatment effect on DSS will be calculated using Gray's method under the competing risk approach, with death due to non-disease related cause treated as the competing risk (Gray 1988). Multivariate analysis on DSS will be performed using the Fine-Gray model, with patient pretreatment characteristics as covariates (Fine 1999).

Will be calculated using the cumulative incidence function for each arm.

Longitudinal analysis will be performed to compare NCF over time between the 2 arms, using the NCF Clinical Trial Battery (CTB) composite score. Early change from baseline in CTB composite score will be evaluated and compared between the 2 arms using 2-sample t tests.

Longitudinal analysis will be performed to compare symptom burden over time between the 2 arms, using the MDASI-BT. Early change from baseline in symptom burden will be evaluated and compared between the 2 arms using 2-sample t tests.

The Kaplan-Meier method will be used to estimate the PFS and OS rates by pHH3 category. The HRs on the effect of pHH3 on PFS and OS, respectively will be calculated using the Cox proportional hazard model and will be tested using the log-rank test. Multivariate analyses will be conducted with patient pretreatment characteristics, such as age and Simpson resection grade, included as covariates.

The number of adverse events will be measured using the CTCAE, version 4

National Cancer Institute (NCI)

NRG Oncology

Symptoms and General Pathology

Atrophy

Conformal focal-brain irradiation using modern radiotherapeutic techniques (i.e., conventionally fractionated VMAT, hypofractionated stereotactic radiotherapy, and proton beam therapy, etc)

The techniques of conformal focal-brain irradiation in the era of modern radiotherapy (i.e., conventionally fractionated VMAT, hypofractionated stereotactic radiotherapy, and proton beam therapy, etc)

Radiation

Chi-Cheng Chuang, M.D.

Shinn-Yn Lin, M.D.

【Background】For cranial-irradiation-naive patients with intracranial meningiomas at risk of local recurrence, the administration of conformal cranial radiotherapy can enhance tumor control in the current era of modern radiotherapeutic techniques. Life expectancy in patients with intracranial meningiomas, particularly non-malignant meningiomas (WHO grade I and II) is essentially similar to people of general population. However, RT-related neurocognitive function (NCF) sequelae are potentially and seriously a concern which should not be ignored. In terms of the natural course of cranial irradiation-induced NCF decline, it might vary considerably according to the specific domains which are selected to be measured. Early neurocognitive decline principally involves impairments of episodic memory, which is significantly associated with functions of the hippocampus. Additionally, the extent of changes in hippocampal volume after local irradiation may be associated with the hippocampal dosimetry. This study thus aims to investigate the potential cause-effect relationship between the hippocampal dosimetry and radiological outcomes represented by the volumetric changes regarding the contralateral hippocampus; furthermore, the correlation between radiological outcomes and neurocognitive endpoints will be examined and clarified.

【Methods】Patients with cranial-RT-naive intracranial meningiomas may be eligible and therefore enrolled in this prospective study addressing both radiological outcomes and neurocognitive endpoints. All eligible and recruited patients should receive baseline volumetric brain MRI examination and baseline neurobehavioral assessment. Subsequently, conformal cranial irradiation in the era of modern radiotherapeutic techniques (including hypofractionated stereotactic radiotherapy, proton beam therapy volumetric modulated arc therapy) will be utilized in order to reduce the dose irradiating the contralateral hippocampus and other relevant organs at risk. The prescribed dose schemes for treating patients with intracranial meningioma depend on the decision of the radiation oncologist in charge and follow the treatment guidelines at our cancer center. Accordingly, a battery of neurocognitive measures, which includes 9 standardized neuropsychological tests categorized into 5 NCF domains (e.g., executive functions, verbal \& non-verbal memory, working memory, psychomotor speed, and amygdala-related emotion recognition), is used to evaluate neurocognitive performances longitudinally for our registered patients. There will be two co-primary outcome measures in the current study. The main primary outcome will be the correlation between the mean hippocampal dose and the extent of change in hippocampal volume at 6 months after the course of cranial RT. The other primary endpoint will be 6-month cognitive-deterioration-free survival.

【Expected Results】This prospective observational cohort study aims to explore and investigate the cause-effect relationship between the hippocampal dosimetry (i.e., mean dose irradiating the hippocampus, particularly the one contralateral to the lateralization of intracranial meningioma) and the extent of hippocampal atrophy signifying one of the measures regarding radiological outcomes. Simultaneously, predefined standardized neurocognitive outcome measures such as hippocampus-related memory functions and amygdala-related emotion recognition will be obtained prospectively and longitudinally in order to examine whether any meaningfully significant correlation exists between the above radiological outcome measures and neurocognitive endpoints. The mutual associations among hippocampal dosimetry, radiological outcomes including the MRI-delineated hippocampal volume, and neurocognitive endpoints including hippocampus-related verbal/non-verbal memory functions will be examined thoroughly.

Cognition-preserving Brain Irradiation for Treating Patients With Intracranial Meningioma in the Era of Modern Radiotherapeutic Techniques Including Proton Beam Therapy - a Prospective Study Focusing on Radiological Outcomes and Neurocognitive Endpoints

Longitudinal changes in the volumes (cc) of the left hippocampus, right hippocampus, left amygdala, right amygdala, left thalamus, right thalamus, and so on based on volumetric MR imaging examinations

Change in verbal memory function related to left hippocampus from baseline to 4 months after cognition-preserving cranial RT

Change in non-verbal memory learning associated with right hippocampus from baseline to 4 months after cognition-preserving brain RT

Change in executive function related to hippocampus from baseline to 4 months after cognition-preserving cranial RT.

Concerning the domain of executive functions generally dominated by the frontal lobes, the Modified Card Sorting Test is employed to assess both conceptual formation and mental shifting which have been documented to be the major components of executive functions.

Change in emotion memory tasks associated with the amygdala from baseline to 4 months after cognition-reserving cranial irradiation.

For evaluate and quantify the cognitive function of amygdala, the NCF test tailored to the emotional recognition task will be used and patients' performances will be assessed using the commercialized and computerized test included in Cambridge Cognition® package.

Change in working memory related to hippocampus from baseline to 4 months after cognition-preserving cranial RT.

Working memory includes executive functions and psychomotor speed.

* The neurocognitive outcome of verbal working memory was determined by the Digit Span Subtest (DS) and Spatial Span (SSP) of the Wechsler Adult Intelligence Scale- 3rd edition (WAIS-III®).
* In order to indicate patients' performance on the psychomotor speed, we make use of Psychomotor Speed Index (PSI), which is derived from the composite score of Digit Symbol Coding Subtest (DSS) and Symbol Searching Subtest (SS) of the WAIS-III®.

Longitudinal changes in the imaging biomarkers from DTI imaging

Longitudinal changes in the fractional anisotropy (FA, unitless index between 0 and 1) from DTI imaging

Trajectories in the imaging biomarker, mean diffusivity (MD, mm squared/second) based on DTI imaging

Chang Gung Memorial Hospital

Neurologic Manifestations

Group will be treated with HBOT for 60 treatments in 3 months.

Control for 3 months without treatment, and then HBOT for 60 treatments in 3 months.

HBOT of 2 ATA for 90 minutes, for 60 treatments

HBOT

Amir Hadanny, MD

Shai Efrati, MD

The aim of the current study is to evaluate, in a prospective cross-over, randomized study, the effect of hyperbaric oxygen therapy (HBOT) on patients with chronic neurological deficits and cognitive impairment after anterior skull base meningioma tumor removal.

Hyperbaric Oxygen Therapy Can Improve Neurological State Post Meningioma Removal Surgery

Hyperbaric Oxygen Therapy Can Improve Neurological State Post Meningioma Removal Surgery -Randomized Prospective Trial

Cognitive function will be assessed using the one-hour Mindstreams Computerized Cognitive Test Battery at baseline, 3 months and 6 months to intervention.

Quality of live will be evaluated by the EQ-5D questionnaire at baseline , 3 months and 6 months to intervention.

Assaf-Harofeh Medical Center

Shai Efrati

Radiotherapy

Laura Fariselli, MD

This is a prospective observational trial consisting of robotic multisession radiosurgery (CyberKnife ®) for large and medium size and/or located at critical site benign intracranial meningiomas.

To date, the treatment of choice for intracranial meningiomas is surgical removal.

Radiotherapy, especially the radiosurgery (SRS), in exclusive, adjuvant or salvage setting represents an alternative or complementary viable treatment to the neurosurgery. Despite being a well-established treatment for intracranial meningiomas, SRS might be associated with significant morbidity when large volumes or critical sites are treated. Hypofractionated stereotactic radiotherapy has the potential to deliver sharply focused high doses per fraction without increasing the risk of toxicity.

The aims of our study are toxicity and symptom control evaluation of radiosurgery treatment delivered in multisession, for large or medium size intracranial meningiomas and/or for intracranial meningioma located at the critical sites (perichiasmatic area, perioptic area, PCA). We will evaluate also the efficacy of the treatment by volumetric analysis of treated meningiomas carrying out a volumetric comparison between pre- and post-radiosurgery treatment (every 6 month after treatment).

The neurological and clinical assessment before and after s-SRS will be based on CTCAE v4.0 and BPN BSN House-Brackman and sensorineural internation scale assessment.

Multisession Radiosurgery in Large Meningiomas

evaluation every 6 months, up to 3 years. Afterwards, every year up to 5 years based on CTCAE v4.0

Evaluation based on 1-3 mm thickness T1 weighted (or volumetric FAT saturation weighted) brain gadolinium-MRI images

Evaluation based on sensorineural international scale

Evaluation based on ophthalmological evaluation

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Observation or Radiation Therapy in Treating Patients With Newly Diagnosed Grade II Meningioma That Has Been Completely Removed by Surgery	NCT03180268	Grade II Mening... Intracranial Me...	Clinical Observ... Radiation Thera...	18 Years -	NRG Oncology
Observation or Radiation Therapy in Treating Patients With Newly Diagnosed Grade II Meningioma That Has Been Completely Removed by Surgery	NCT03180268	Grade II Mening... Intracranial Me...	Clinical Observ... Radiation Thera...	18 Years -	NRG Oncology
Cognition-preserving Brain Irradiation for Treating Patients With Intracranial Meningioma in the Era of Modern Radiotherapeutic Techniques Including Proton Beam Therapy - a Prospective Study Focusing on Radiological Outcomes and Neurocognitive Endpoints	NCT05832099	Intracranial Me...	Radiation	18 Years - 85 Years	Chang Gung Memorial Hospital
Hyperbaric Oxygen Therapy Can Improve Neurological State Post Meningioma Removal Surgery	NCT02084927	Intracranial Me... Neurologic Defi...	HBOT	18 Years -	Assaf-Harofeh Medical Center
Observation or Radiation Therapy in Treating Patients With Newly Diagnosed Grade II Meningioma That Has Been Completely Removed by Surgery	NCT03180268	Grade II Mening... Intracranial Me...	Clinical Observ... Radiation Thera...	18 Years -	NRG Oncology
Multisession Radiosurgery in Large Meningiomas	NCT02974127	Intracranial Me...	Radiotherapy	18 Years - 80 Years	Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
Multisession Radiosurgery in Large Meningiomas	NCT02974127	Intracranial Me...	Radiotherapy	18 Years - 80 Years	Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta

Spots Global Cancer Trial Database for intracranial meningioma