radiosurgery with or without whole-brain radiation therapy in treating patients with brain metastases

Conditions: Metastatic Cancer

Summary: rationale: radiation therapy uses high-energy x-rays to damage tumor cells. radiosurgery may be able to deliver x-rays directly to the tumor and cause less damage to normal tissue. it is not yet known if radiosurgery is more effective with or without whole-brain radiation therapy in treating brain metastases. purpose: randomized phase iii trial to compare the effectiveness of radiosurgery with or without whole-brain radiation therapy in treating patients who have 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.

Eligibility criteria:
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

Keywords: tumors metastatic to brain