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Conformal whole brain radiotherapy with unilateral hippocampal avoidance and Concurrent use of Memantine HCL

Conformal whole brain radiotherapy with bilateral hippocampal avoidance and Concurrent use of Memantine HCL

Conformal Whole Brain Radiotherapy 30 Gy in 10 fractions with Unilateral Hippocampal Avoidance using Intensity modulated radiotherapy, Volumetric arc therapy, or Tomotherapy

Conformal Whole Brain Radiotherapy with Unilateral Hippocampal Avoidance

Conformal Whole Brain Radiotherapy 30 Gy in 10 fractions with Bilateral Hippocampal Avoidance using Intensity modulated radiotherapy, Volumetric arc therapy, or Tomotherapy

Conformal Whole Brain Radiotherapy with Bilateral Hippocampal Avoidance

Start from day 1 of WBRT orally for 24 weeks and escalating doses over the first 4 weeks

Memantine Hydrochloride

Feng-Ming Hsu, MD, PhD

Feng-Ming Hsu, MD

Brain metastases are the most common brain tumors in adults. It is estimated that around 10-30% of cancer patients would develop brain metastases during the course of their illness.

Whole brain radiotherapy (WBRT) is the treatment of choice for the majority of patients with brain metastases. WBRT yields high radiologic response rate (27\~56%) and is effective in rapid palliation of neurologic symptoms as well as prolongs time to neurocognitive function decline caused by intracranial lesions. By using conventional fractionation, more than one- third of patients developed late neurocognitive toxicity while memory impairment was the most common symptom. The incidence is even higher when a formal and sensitive neurocognitive assessment was prospectively evaluated. With more long-term survivors nowadays, it has become increasingly important to minimize neurocognitive function decline and maintain quality of life in patients with brain metastasis.

The function of hippocampus is cooperation in learning, consolidation and retrieval of information and essential for formation of new memories. Bilateral and unilateral radiation injury of the hippocampus is known to alter learning and memory formation. Several preclinical studies support the hypothesis of hippocampus-mediated cognitive dysfunction by ionizing radiation. Clinical studies show increase in radiation dose to hippocampus is associated with subsequent neurocognitive function impairment in adult and pediatric patients. Furthermore, the result of phase III randomized trials suggested hippocampal avoidance plus Memantine significantly reduce the risk of neurocognitive impairment at 6 months from 68.2% in control arm with standard WBRT to 59.5% in experimental arm. In the investigator's prior investigation, patients received conformal WBRT with bilateral hippocampal avoidance also had significant less declines in verbal memory at 6 months.

Previous studies showed the right and left hippocampus exert different neurocognitive functions. Several retrospective studies also demonstrated that the radiation dose to the left hippocampus is more related to neurocognitive impairment. Planning study and investigation showed that by avoiding the left hippocampus alone, the radiation dose to the spared unilateral hippocampus is further decreased. In present study, a single blind randomized phase II trial is designed to investigate the effectiveness of neurocognitive function preservation using conformal WBRT with bilateral or unilateral hippocampal avoidance and memantine.

Neurocognitive Outcome of Bilateral or Unilateral Hippocampal Avoidance WBRT With Memantine for Brain Metastases

Neurocognitive Outcome of Conformal Whole Brain Radiotherapy With Bilateral or Unilateral Hippocampal Avoidance Plus Memantine for Brain Metastases: A Phase II Single Blind Randomized Trial

Number of participants with Genomic risk of neurocognitive impairment after WBRT

Decline in Hopkins Verbal Learning Test-Revised (HVLT-R) memory score (sum of total recall and recognition index) from baseline to 6 months after the start of conformal whole brain radiotherapy (WBRT) with bilateral or unilateral hippocampal avoidance for multiple brain metastases. HVLT-R Total recall raw scores ranged from 0 to 36, recognition index ranged from 0 to 12. The higher the score indicated better short term memory preservation

Evaluate neurocognitive function by a standardized neurocognitive battery Hopkins Verbal Learning Test-Revised (HVLT-R) with Total recall score (range from 0 to 36), delayed recall score (range from 0 to 12) and recognition index (range from 0 to 12). The higher the score indicated better short term memory preservation.

Evaluate neurocognitive function by a standardized neurocognitive battery Trail Making Test Part A \& B. TMT-A and B tested the executive function documented with time needed for complete test with no upper limit of range. The longer the time needed, the worse executive function patients preserved.

Evaluate neurocognitive function by a standardized neurocognitive battery Controlled Oral Word Association Test. Patients are given one phoneme at a time and instructed to say aloud as many words beginning with that phoneme as they could within 1 minute, for a total of three phonemes in 3 minutes. The more the words patients able to say in limit time, the better outcome presented.

EORTC Quality of Life-Core 30 questionnaire module (at question 1 to 27, range from 1 to 4; at question 29 and 30, range from 1 to 7) Quality of Life questionnaire-Brain.

Function Assessment Cancer Therapy for patients with Cognitive function issue

Common Toxicity Criteria for Adverse Events version 4

Number of participant with intracranial progression on MRI of brain

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Neurocognitive Outcome of Bilateral or Unilateral Hippocampal Avoidance WBRT With Memantine for Brain Metastases	NCT04801342	Metastatic Mali...	Conformal Whole... Conformal Whole... Memantine Hydro...	20 Years -	National Taiwan University Hospital
Neurocognitive Outcome of Bilateral or Unilateral Hippocampal Avoidance WBRT With Memantine for Brain Metastases	NCT04801342	Metastatic Mali...	Conformal Whole... Conformal Whole... Memantine Hydro...	20 Years -	National Taiwan University Hospital

Spots Global Cancer Trial Database for conformal whole brain radiotherapy with unilateral hippocampal avoidance