Radiosurgery With or Without Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases

OBJECTIVES:

- Compare the overall survival of patients with 1 to 3 cerebral metastases treated with
radiosurgery with or without whole brain radiotherapy.

- Compare the time to CNS failure (brain) in patients treated with these regimens.

- Compare the quality of life, duration of functional independence, and long-term
neurocognitive status in patients treated with these regimens.

- Compare the post-treatment toxic effects of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age
(60 and over vs under 60), extracranial disease (controlled for more than 3 months vs
controlled for 3 months or less), and number of brain metastases (1 vs more than 1).
Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients undergo radiosurgery.

- Arm II: Patients undergo radiosurgery. Within 14 days, patients then undergo whole
brain radiotherapy 5 days a week for 2.5 weeks.

Quality of life is assessed at baseline, the beginning of each treatment, at week 6, every 3
months for 1 year, every 4 months for 1 year, and then every 6 months for 2 years.

Patients are followed at weeks 6 and 12, every 3 months for 9 months, every 4 months for 1
year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 480 patients (240 per treatment arm) will be accrued for this
study within 5 years.

Inclusion Criteria:

- Diagnosis of cerebral metastases meeting all of the following requirements:

- 1-3 de novo lesions

- Metastases must be from a histologically confirmed extracerebral primary site,
another metastatic site, or from the metastatic brain lesion(s)

- Each lesion must be less than 3.0 cm by contrasted MRI of the brain

- Lesions must not be within 5 mm of optic chiasm or within the brainstem

- No primary germ cell tumor, small cell carcinoma, or lymphoma

- No leptomeningeal metastases

- Eligible for treatment with gamma knife or linear accelerator-based radiosurgery

- Performance status - ECOG 0-2

- Performance status - Zubrod 0-2

- Not pregnant

- Negative pregnancy test

- Fertile patients must use effective contraception

* Male patients must continue to use contraception for 3 months after the completion
of radiotherapy

- No pacemaker or other MRI-incompatible metal in body

- No known allergy to gadolinium

- Deemed to be at low risk for recurrence from any prior malignancies

- At least 7 days since prior chemotherapy

- Concurrent hormonal agents allowed

- Concurrent steroids allowed

- No prior cranial radiotherapy

- No prior resection of cerebral metastasis

- Concurrent anticonvulsants allowed provided therapeutic serum/plasma level maintained
before study intervention