Clinical trial NCT05807165: HF-SRT vs. HS-WBRT in Treating Patients With Brain Oligometastases
Official title: Hypofractionated Stereotactic Radiotherapy Versus Hippocampus-sparing Whole-brain Radiotherapy in Treating Cancer Patients With Brain Oligometastases: A Phase II Parallel Non-randomized and Prospective Observational Study
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Brain Oligometastases
Keywords: Brain Oligometastases
Stereotactic Radiotherapy (SRT)
Hypofractionation
Hypofractionated Stereotactic Radiotherapy (HF-SRT)
Hippocampus
Hippocampus-Sparing Whole-Brain Radiotherapy (HS-WBRT)
Neurocognitive Functions (NCFs)
Central Nervous System (CNS)
Progression-free Survival (PFS)
CNS Progression-Free Survival (CNS-PFS)
Patterns of CNS Failure
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
First posted: 2023-04-11
Enrollment: 115
Sex: ALL
Minimum age (years): 20
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with newly-diagnosed brain oligometastases and an acceptable performance status would receive baseline neurocognitive assessment.

Brief summary: \[Background\] 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.


Eligibility criteria: Inclusion Criteria:

* Patients with pathologically-confirmed non-hematopoietic malignancy who are referred for postoperative adjuvant or therapeutic hypofractionated stereotactic radiotherapy (HF-SRT)
* A Fair/good performance status no worse than Eastern Cooperative Group (ECOG) of 2 or an acceptable performance status of Karnofsky Score (KPS) at least 70
* The number and extent of brain metastatic lesions should be no more than three metastatic foci with a greatest diameter no more than 4 cm shown on pre-radiotherapy MRI; namely, that is the clinical setting of oligometastatic brain disease or brain oligometastases

Exclusion Criteria:

* Patients with their primary cancer arising from hematological malignancies (i.e., malignant lymphomas, leukemia), germ cell tumors, or malignant meningiomas
* Patients with MRI-identified metastasis within 5 mm peri-hippocampally
* Patients with metastasis involving the brain stem
* Clinical suspicion of leptomeningeal spreading
* History of prior radiotherapy including stereotactic radiosurgery delivered to brain/head region for any reasons

Primary outcomes:
measure: CNS progression-free survival (CNS-PFS)
timeFrame: The time from study enrollment to CNS disease progression of death from any cause, assessed up to 10 years.
measure: Cognitive-deterioration-free survival (CD-free survival)
timeFrame: 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.
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: The time from enrollment to death, assessed up to 10 years.
measure: Median survival time (MST)
timeFrame: The time from enrollment to death, assessed up to 10 years.
measure: Causes of death (neurologic vs non-neurologic death)
timeFrame: The time from enrollment to death, assessed up to 10 years.
measure: Patterns of CNS (Intracranial or Leptomeningeal Disease) failure evaluated through brain MRI
timeFrame: The time from enrollment to CNS failure, assessed up to 10 years.
measure: Time to progression (TTP)
timeFrame: The time from enrollment to CNS progression, assessed up to 10 years.
measure: Progression-free survival (PFS)
timeFrame: The time from enrollment to disease progression, assessed up to 10 years.
Other outcomes:
Locations:
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital
Study officials:
References: