An observational study in Brain Oligometastases, sponsored by Chang Gung Memorial Hospital. Not yet recruiting at 1 site in Taiwan. Open to participants aged 20 Years to 85 Years. Per ClinicalTrials.gov, last updated 2023-04-11.
Sponsored by Chang Gung Memorial Hospital · Observational
[Background] For newly-diagnosed patients with brain metastases (BMs), conventional whole-brain radiotherapy (WBRT) might still remain a common palliative management. However, WBRT-related late consequences, particularly a decline in neurocognitive functions (NCFs), are a major concern. Actually, WBRT-related neurocognitive dysfunction is usually characterized as deterioration involving learning and memory, in which the extremely radiosensitive hippocampus indeed plays a critical role.
To postpone the occurrence and mitigate neurocognitive impairments associated with conventional WBRT, there have been some strategies in the clinical practice of radiation oncology. Among them, the technology/technique of highly precise/accurate stereotactic radiosurgery or stereotactic radiotherapy (i.e., hypofractionated stereotactic radiotherapy, HS-SRT) might have been widely administered in irradiating exclusively the focal brain metastatic lesions, particularly in cancer patients with a limited number of brain metastases. By contrast, the planning strategy of hippocampus avoidance during the course of whole-brain irradiation has also been well-established in preserving NCFs.
[Methods] Newly-diagnosed cancer patients harboring 1 - 4 brain metastatic lesions are eligible if they still have fair/good performance status. Eligible and enrolled should receive baseline brain MRI examination and pre-WBRT neurocognitive assessment. Although non-randomized, this phase II trial comprises two prospective (radiotherapeutic) cohorts with individually different planning techniques and prescription schedules. Cohort I represents patients referred for arranging partial-brain irradiation; namely, a course of hypofractionated stereotactic radiotherapy (HF-SRT) is delivered within 2 weeks with a cumulative dose of 3000 - 3500 cGy in 5 fractions. By contrast, Cohort II stands for patients referred for arranging the course of hippocampus-sparing WBRT (HS-WBRT), delivered within 3 weeks with a cumulative dose of 3000 cGy in 12 fractions, during which the planning technique of simultaneous integrated boost (SIB) is employed to focally escalate the dose irradiating the brain metastatic foci. Besides, adhering to several international clinical practice guidelines, the synergic use of the neuroprotective agent (memantine) will be routinely applied in the treatment Cohort II (HS-WBRT). In both treatment cohorts, a battery of neuropsychological measures, which includes 7 standardized neuropsychological tests (e.g., executive functions, verbal and non-verbal memory, working memory, and psychomotor speed), is used to evaluate neurocognitive functions.
The primary outcome measure is the median time of CNS progression-free survival (CNS-PFS). Secondary outcome measures encompass both neuro-oncological endpoints and neurocognitive endpoints, among which there is cognitive-deterioration-free survival (CD-free survival). CD-free survival is defined mainly as the time from enrollment to a NCF decline of exceeding than 1 SD away from the baseline involving at least one of the assessed NCF tests. Additionally, patients who expire before 6 months or are alive but fail to undergo all the neurocognitive testing administered would also be defined as suffering from cognitive deterioration.
[Expected results] This prospective observational study aims to examine thoroughly and analyze the comparatively between the two radiotherapeutic cohorts (HF-SRT versus HS-WBRT), addressing both CNS tumor control and neurocognitive functional outcomes. It is expected that the patterns of (CNS) failure and individual time to progression will be clearly demonstrated in this prospective observational study encompassing two distinct radiotherapeutic cohorts.
Chang Gung Memorial Hospital is the lead sponsor of 1,064 studies on the registry; 235 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Patients with newly-diagnosed brain oligometastases and an acceptable performance status would receive baseline neurocognitive assessment.
Exclusion Criteria:
RT techniques and the dose schemes in the cohort of Hypofractionated Stereotactic Radiotherapy (HF-SRT)
Radiation: Hypofractionated Stereotactic Radiotherapy (HF-SRT)
The course of hippocampus-sparing whole-brain radiotherapy (HS-WBRT) combined with the synergic use of the neuroprotective agent, memantine
Radiation: Hippocampus-Sparing Whole-Brain Radiotherapy (HS-WBRT) plus memantine
The administered dose-fractionation schemes range between 30 and 35 Gy delivered within two weeks with a dose per fractionation ranging from 6 to 7 Gy.
* The prescribed dose is 30 Gy delivered in 12 fractions for therapeutic or adjuvant WBRT. * The prescription of memantine for finally twice-daily dosing will be prescribed as follows: * During the first 3 weeks concurrent with the delivery of hippocampus-sparing WBRT, 5-mg morning dose will be initially prescribed \[Week 1 -3\] * 5-mg twice a day in the following week \[Week 4\] * A morning dose of 10 mg and an evening dose of 5 mg in the following week \[Week 5\] * 10-mg twice a day for the subsequent weeks up to Week 24 \[Week 6 - 24\]
CNS progression-free survival (CNS-PFS)
The median CNS progression-free survival (CNS-PFS), which is a time-dependent endpoint, defined as the time from study enrollment to CNS disease progression of death from any cause.
Time frame: The time from study enrollment to CNS disease progression of death from any cause, assessed up to 10 years.
Cognitive-deterioration-free survival (CD-free survival)
The time from enrollment to a cognitive decline of exceeding more than 1SD away from the baseline in at least one of the assessed NCF tests. Furthermore, regarding cognitive-deterioration-free survival, patients who expire before 6 months or are alive but do not undergo all the neurocognitive testing administered or even fail to receive MMSE evaluation would be assumed reasonably that they suffer cognitive deterioration at the time of death or at the time point, or they fail to receive their first neurocognitive assessment follow-up as long as there are no subsequent NCF assessments.
Time frame: The time from enrollment to a cognitive decline of exceeding more than 1SD away from the baseline in at least one of the assessed NCF tests, assessed up to 24 months.
Overall survival (OS)
Time frame: The time from enrollment to death, assessed up to 10 years.
Median survival time (MST)
Time frame: The time from enrollment to death, assessed up to 10 years.
Causes of death (neurologic vs non-neurologic death)
Time frame: The time from enrollment to death, assessed up to 10 years.
Patterns of CNS (Intracranial or Leptomeningeal Disease) failure evaluated through brain MRI
Three patterns of central nervous system (CNS) failure were classified particularly when the CNS progression in the corresponding patient manifests for the first time after the course of HF-SRT: intracranial local failure (LF), distant brain parenchymal failure (DPF), and development of leptomeningeal disease (LMD).
Time frame: The time from enrollment to CNS failure, assessed up to 10 years.
Time to progression (TTP)
Time to CNS progression
Time frame: The time from enrollment to CNS progression, assessed up to 10 years.
Progression-free survival (PFS)
Intracranial PFS or CNS progression-free survival; CNS progression-free survival
Time frame: The time from enrollment to disease progression, assessed up to 10 years.
This study is not yet recruiting, as verified in Dec 2022. You cannot join it, but the record below documents what was studied.
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Chang Gung Memorial Hospital