Neuropsychological Changes in Patients Receiving Radiation Therapy for Brain Metastases

Background:

- Metastatic brain tumors occur more frequently than primary brain tumors and occur in
approximately 25 percent of patients who die of cancer each year.

- The Radiation Therapy Oncology Group (RTOG) developed three prognostic classes using a
recursive partitioning analysis (RPA) of a large database. Theses classes are based on
Karnofsky Performance Status (KPS), age and disease status.

- The RTOG RPA classes do not include neuropsychological function as a measure of outcome.

- There is no consensus of standardization of test selection to measure changes in
neuropsychological functioning in this patient population.

- Neuropsychological function has an important effect on quality of life and should be
included when determining prognosis and treatment options for patients.

- Neuropsychological functioning is important when determining the effects of treatments
and for measuring outcomes in clinical trials.

Objectives:

- To identify the neuropsychological test scores which detect significant change in
neuropsychological functioning in patients receiving radiation therapy for brain
metastases.

- To examine the relationship between neuropsychological function and survival in patients
receiving radiation therapy for brain metastases.

Eligibility:

- Patients age 18 years and older.

- Pathologically confirmed primary malignancy with at least one intraparenchymal brain
metastasis as identified on brain MRI scan with intravenous contrast.

- The patient must communicate in English in order to complete the neuropsychological
evaluations.

Design:

- This is a longitudinal study that will administer serial neuropsychological assessments
to patients with brain metastases who receive radiation therapy.

- Patients will undergo a battery of neuropsychological tests prior to radiotherapy (WBRT
or WBRT followed by SRS), and then after radiation at one month post-baseline (2 weeks
after radiation therapy), then at 3, and 6 months, and then every 3 months for up to 12
months after baseline.

- The test battery will involve approximately 40 minutes of direct cognitive testing and
15 minutes of questionnaires.

There will be three cohorts of 20 patients each for a total of 60 patients. The three cohorts
will be made up of differing histologies and will be sorted on the basis of their RTOG RPA
Class.

-INCLUSION CRITERIA:

1. Patients must be 18 years of age or older.

2. Pathologically confirmed primary malignancy with at least one intraparenchymal brain
metastasis as identified on brain MRI scan with intravenous contrast.

- Cohort 1 (N=20): KPS greater than 70; Age less than or equal to 65; controlled
primary tumor and no extracranial metastases.

- Cohort 2 (N=20): KPS greater than 70 and at least one of the following: age
greater than 65, uncontrolled or synchronous primary disease, or extracranial
metastases

- Cohort 3 (N=20): KPS less than 70

3. Patient must have a primary medical or surgical oncologist in the community or at NCI
who is willing to collaborate with the ROB staff in the clinical management of the
patient.

4. All patients must sign a document of informed consent indicating their understanding
of the investigational nature and the risks of this study BEFORE any of the protocol
related studies are preformed (this does not include routine laboratory tests or
imaging studies required to establish eligibility).

5. Subjects of childbearing or child- fathering potential must be willing to use a
medically acceptable form of birth control, which includes abstinence, while they are
being treated on this study.

EXCLUSION CRITERIA:

1. Cognitively impaired patients who cannot give informed consent, including patients
assigned a power of attorney for medical decisions.

2. Inability to communicate in the English language.

3. Pre- existing or active psychiatric or neurologic impairments, not caused by the brain
metastasis, which, in the opinion of the investigators, will interfere with the proper
administration or completion of the protocol.

4. Prior Therapy

- Patients must not have been treated for a previous brain metastasis.

- Patients must not have had previous cranial radiation.

- Patients must not undergo treatment with an investigational drug for the primary
disease within 7 days of baseline neuropsychological testing.

- Patients must not receive systemic therapy within 7 days prior to baseline
neuropsychological testing.

- Patients who have had surgery for their current brain metastasis must wait at
least 7 days before baseline neuropsychological testing.

5. Concurrent Therapy

- Treatment of primary malignancy with systemic therapy (chemotherapy or biologic
agents) cannot be delivered concurrently with the treatment of the intracranial
disease. However, treatment of the primary site with local therapy, either
surgery or radiotherapy, can be performed concurrently with the treatment of the
intracranial disease.

- Patients receiving glucocorticoids should be tapered to the lowest possible dose,
or stopped altogether, by the treating physician. If glucocorticoid dose is
adjusted or given for the first time, the patient must remain on stable dose of
glucocorticoids for at least 24 hours prior to initial neurocognitive testing, CT
and MR imaging.

6. Patients needing emergent radiation therapy for their brain metastases will be
excluded

7. Patients must not have evidence of leptomeningeal metastases.

8. Patients must not be HIV positive.

9. Other medical conditions deemed by the PI or associates to make the patient ineligible
for protocol investigations.

10. Pregnant or breast-feeding females are excluded because of the potential mutagenic
effects on a developing fetus or newborn.

11. Clinically significant unrelated systemic illness which in the judgment of the
Principal or Associate Investigator would compromise the patient s ability to tolerate
this therapy or are likely to interfere with the study procedures or results.