Clinical trial NCT05832099: 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
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
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Intracranial Meningioma
Keywords: Intracranial Meningioma
Radiation Therapy
Magnetic Resonance Image (MRI)
Volumetric MRI
Functional MRI (fMRI)
Radiological Outcomes
Hippocampus
Neurocognitive Functions (NCFs)
Cognition-Preserving Brain Radiotherapy
Proton Beam Radiotherapy
Hippocampal Atrophy
Amygdala
Thalamus
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
First posted: 2023-04-27
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with clinically or pathologically-confirmed intracranial non-malignant meningiomas referred for arranging conformal focal-brain irradiation using modern radiotherapeutic techniques including volumetric modulated arc therapy (VMAT), hypofractionated stereotactic radiotherapy (SRT), and proton beam therapy.

Brief 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Longitudinal changes in the volumes of organs at risk including the hippocampus
timeFrame: baseline (pre-RT), 4 months, 8-10 months (optional), 12 months, 18 months, 24 months
Secondary outcomes:
measure: Change in verbal memory function
timeFrame: baseline (pre-RT), 4 months, 8-10 months (optional), 12 months, 18 months, 24 months
measure: Change in non-verbal memory learning
timeFrame: baseline (pre-RT), 4 months, 8-10 months (optional), 12 months, 18 months, 24 months
measure: Change in executive function
timeFrame: baseline (pre-RT), 4 months, 8-10 months (optional), 12 months, 18 months, 24 months
measure: Change in emotion memory task
timeFrame: baseline (pre-RT), 4 months, 8-10 months (optional), 12 months, 18 months, 24 months
measure: Change in working memory
timeFrame: baseline (pre-RT), 4 months, 8-10 months (optional), 12 months, 18 months, 24 months
measure: Longitudinal changes in the imaging biomarkers
timeFrame: baseline (pre-RT), 4 months, 8-10 months (optional), 12 months, 18 months, 24 months
measure: Longitudinal changes in the fractional anisotropy
timeFrame: baseline (pre-RT), 4 months, 8-10 months (optional), 12 months, 18 months, 24 months
measure: Trajectories in the imaging biomarker
timeFrame: baseline (pre-RT), 4 months, 8-10 months (optional), 12 months, 18 months, 24 months
Other outcomes:
Locations:
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital
Study officials:
References: