Memory Preservation of Hippocampal Avoidance Whole Brain Radiotherapy

Study Overview
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Brief Summary
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The study aimed to investigate the memory preservation and neurocognitive function protection of hippocampal avoidance whole brain radiotherapy (HA-WBRT) among people who speak Mandarin Chinese or Taiwanese.

Detailed Description
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Brain metastasis is very common, about 30% incidence rate for all patients with a diagnosis of cancer. The rising incidence of brain metastasis is most likely due to recent advances in systemic therapy, and use of magnetic resonance imaging (MRI). The most common primary site is the lung followed by breast. One of the standard treatments is whole brain radiotherapy; it can prolong the decline of neurocognitive function and improve quality of life. However, it can also cause decline in neurocognitive function as a late sequela. Memory impairment is the main cognitive function that affected by radiotherapy, and the neuronal stem cells located at hippocampal subgranular zone are highly sensitive to radiotherapy. There have been large randomized trials confirming that by HA-WBRT, the neurocognitive function decline can be reclaimed. In Taiwan, HA-WBRT is a popular and emerging treatment. However, not much study focused on its effects on neurocognitive function. The study is aimed to objectively investigate the memory preservation and neurocognitive function protection of HA-WBRT in people speaking Mandarin Chinese or Taiwanese by utilizing neurocognitive function test and QoL questionnaire.

Official Title
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The Memory Preservation Study of Whole Brain Radiotherapy With Hippocampal Avoidance for Patients With Brain Metastases

Conditions
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Brain Metastases, Neurocognitive Function

Intervention / Treatment
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* Radiation: Hippocampal avoidance whole brain radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with brain metastases, the brain metastases are located 5mm outside the hippocampus Pathologically proven diagnosis of nonhematopoietic malignancy other than germ cell malignancy No psychologic disorders Radiation Therapy Oncology Group recursive partitioning analysis class I or II First or second language: Mandarin Chinese or Taiwanese Signed the inform consensus Exclusion Criteria: Less than 20 years old Leptomeningeal metastases or hydrocephalus Previous radiotherapy to head and neck region Creatinine >1.5mg/dl More than 2 extracranial metastases Patients who cannot tolerate memory or neurocognitive function test or cannot complete QoL questionnaire

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Interventional Model Description: Hippocampal avoidance -whole brain radiotherapy(HA-WBRT), which delivers radiation to whole brain and moreover, to reduce mean dose to hippocampal neural stem-cell compartment to minimize the neurocognitive function impairment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: HA-WBRT<br>Patients with brain metastases outside a 5-mm margin around either hippocampus and are eligible to this study will receive hippocampal avoidance whole brain radiotherapy 30 gray (Gy) in 10 fractions. The primary endpoint is Wechsler Memory Scale (Chinese) and cognitive abilities screening instrument (CASI) at 4 months. | Radiation: Hippocampal avoidance whole brain radiotherapy<br>* Planning target volume(PTV) for whole brain is Whole brain parenchyma plus2mm margin excluding metastases and HA region, 30Gy in 10 fractions will be delivered to PTVwhole brain. Bilateral Hippocampus will be contoured according to Radiation Therapy Oncology Group 0933 and hippocampal avoidance region is Hippocampi + 5mm margin. According to Radiation Therapy Oncology Group 0933 trial, dose to 100% of the hippocampus could not exceed 9 Gy, and maximal hippocampal dose could not exceed 16 Gy; dose to 100% of the hippocampus exceeding 10 Gy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of Memory immediate recall and delayed recall | The memory battery is using Wechsler Memory Scale (Chinese), including Logical Memory I & II, Word Lists Ⅰ & II, Faces Ⅰ and spatial span. | From baseline to 4 months after RT complete, tests are performed at baseline before radiotherapy begins, 2 months after radiotherapy complete and 4 months after radiotherapy complete. | 
| Changes of general cognitive function | General cognitive function are tested using cognitive abilities screening instrument, CASI for screening and to test cognitive function as a whole. | From baseline to 4 months after RT complete, tests are performed at baseline before radiotherapy begins, 2 months after radiotherapy complete and 4 months after radiotherapy complete. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of Quality of life | Quality of life are assessed using The Functional Assessment of Cancer Therapy-Brain (FACT-Br) questionnaire | From baseline to 4 months after RT complete, the participants are requested to fill in the questionnaire of quality of life at baseline before radiotherapy begins, and 2 months after radiotherapy complete and 4 months after radiotherapy complete. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hippocampal avoidance whole brain radiotherapy (HA-WBRT), brain metastases, memory preservation, neurocognitive function