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

Intracranial Meningioma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05832099
• Other study ID #: 202202092A3
• Status: Not yet recruiting
• Start date: August 1, 2023
• Est. completion date: July 31, 2026

Study information

• Verified date: December 2022
• Source: Chang Gung Memorial Hospital
• Contact: Chi-Cheng Chuang, M.D.
• Phone: +88633281200
• Email: ccc2915[@]cgmh.org.tw
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

【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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 74
• Est. completion date: July 31, 2026
• Est. primary completion date: July 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Patients with clinically or pathologically-confirmed intracranial non-malignant meningiomas who are at least 18 years old, referred for arranging conformal radiotherapy
• A Fair/good performance status superior to Eastern Cooperative Group (ECOG) of 2 or an acceptable performance status of Karnofsky Score (KPS) at least 70

Exclusion Criteria:

• History of prior radiotherapy delivered to brain/head region for any reason, including stereotactic radiosurgery
• Patients with malignant meningiomas diagnosed pathologically (WHO grade III)
• Patients with presumed clinical target volume (CTV) encompassing bilateral peri-hippocampal regions within 5 mm away from the adjacent periphery of the hippocampus
• Patients whose quality of volumetric MRI fails to meet the minimal requirements for physicians to delineate the hippocampal contouring (i.e., slice thickness > 2mm)

Related Conditions & MeSH terms

• Intracranial Meningioma
• Meningioma

Intervention

Radiation:
• Radiation
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)

Locations

Country	Name	City	State
Taiwan	Chang Gung Memorial Hospital	Taoyuan

Sponsors (1)

Lead Sponsor	Collaborator
Chang Gung Memorial Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Longitudinal changes in the volumes of organs at risk including the hippocampus	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	baseline (pre-RT), 4 months, 8-10 months (optional), 12 months, 18 months, 24 months
Secondary	Change in verbal memory function	Change in verbal memory function related to left hippocampus from baseline to 4 months after cognition-preserving cranial RT	baseline (pre-RT), 4 months, 8-10 months (optional), 12 months, 18 months, 24 months
Secondary	Change in non-verbal memory learning	Change in non-verbal memory learning associated with right hippocampus from baseline to 4 months after cognition-preserving brain RT	baseline (pre-RT), 4 months, 8-10 months (optional), 12 months, 18 months, 24 months
Secondary	Change in executive function	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.	baseline (pre-RT), 4 months, 8-10 months (optional), 12 months, 18 months, 24 months
Secondary	Change in emotion memory task	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.	baseline (pre-RT), 4 months, 8-10 months (optional), 12 months, 18 months, 24 months
Secondary	Change in working memory	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®.	baseline (pre-RT), 4 months, 8-10 months (optional), 12 months, 18 months, 24 months
Secondary	Longitudinal changes in the imaging biomarkers	Longitudinal changes in the imaging biomarkers from DTI imaging	baseline (pre-RT), 4 months, 8-10 months (optional), 12 months, 18 months, 24 months
Secondary	Longitudinal changes in the fractional anisotropy	Longitudinal changes in the fractional anisotropy (FA, unitless index between 0 and 1) from DTI imaging	baseline (pre-RT), 4 months, 8-10 months (optional), 12 months, 18 months, 24 months
Secondary	Trajectories in the imaging biomarker	Trajectories in the imaging biomarker, mean diffusivity (MD, mm squared/second) based on DTI imaging	baseline (pre-RT), 4 months, 8-10 months (optional), 12 months, 18 months, 24 months