Neurocognitive Outcome of Conformal WBRT w/wo Hippocampal Avoidance for Brain Metastases

Inclusion criteria:

To be eligible for inclusion, patients must fulfill the following criteria:

1. Patients with a histologic diagnosis of non-hematopoietic malignancy and radiographic evidence of brain metastases
2. Patients with brain metastasis outside a 5-mm margin around either hippocampus on gadolinium contrast enhanced MRI obtained within 30 days prior to registration
3. Patients with brain metastasis who have not been or will not be treated with stereotactic radiosurgery (SRS) or have received SRS for≤ 5 intracranial metastatic lesions
4. No evidence of leptomeningeal metastasis on gadolinium-enhanced MRI within 30 days prior registration
5. Age ≥ 20 years
6. Karnofsky Performance Status ≥ 60%
7. Life expectancy of ≥ 4 months.
8. Women of childbearing potential and male participants must practice adequate contraception
9. Patients must be able to comply with the study protocol and follow-up schedules and provide study- specific informed consent

Exclusion criteria:

Patients fulfill any of the following criteria will be excluded from this trial

1. Prior radiotherapy to brain or SRS to \> 5 intracranial metastatic lesion(s) or the biological equivalent dose in 2-Gy fractions was greater than 7.3 Gy to 40% of the volume of bilateral hippocampus from prior SRS
2. Serum creatinine \> 2.0 mg/dL within 30 days prior registration
3. Contraindication to MRI such as implanted metal devices or foreign bodies, severe claustrophobia
4. Patients with leptomeningeal metastases
5. Severe, active comorbidities which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and adverse events of the protocol, or limit compliance with study requirements, defined as follows:

   1. Uncontrolled active infection requiring intravenous antibiotics at the time of registration
   2. Transmural myocardial infarction ≤ 6 months prior to registration
   3. Unstable angina or congestive heart failure requiring hospitalization ≤ 6 months prior to registration
   4. Life-threatening uncontrolled clinically significant cardiac arrhythmias
   5. Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
   6. Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
   7. Uncontrolled psychiatric disorder
   8. Uncontrolled, clinically significant cardiac arrhythmias
6. Will receive any other investigational agent or chemotherapy and/or target therapies during WBRT
7. Women of childbearing potential and male participants who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the radiation treatment involved in this study may be significantly teratogenic