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