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

Alliance for Clinical Trials in Oncology213 enrolled

Overview

RATIONALE: Stereotactic radiation therapy can send x-rays directly to the tumor and cause less damage to normal tissue. Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known whether stereotactic radiation therapy is more effective with or without whole-brain radiation therapy in treating patients with brain metastases. PURPOSE: This randomized phase III trial is studying stereotactic radiation therapy and whole-brain radiation therapy to see how well they work compared with stereotactic radiation therapy alone in treating patients with brain metastases.

OBJECTIVES: Primary * Compare the overall survival of patients with 1 to 3 cerebral metastases treated with stereotactic radiosurgery with vs without whole-brain radiotherapy. Secondary * Compare time to CNS (brain) failure in patients treated with these regimens. * Compare quality of life, duration of functional independence, and long-term neurocognitive status of patients treated with these regimens. * Compare post-treatment toxicity in these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (18 to 59 vs 60 and over), extracranial disease (controlled for ≤ 3 months vs controlled for \> 3 months), and number of brain metastases (1 vs 2 vs 3). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients undergo stereotactic radiosurgery (SRS). * Arm II: Patients undergo SRS as in arm I. Within 14 days, patients then undergo whole-brain radiotherapy 5 days a week for 2.5 weeks. Quality of life, functional independence, and neurocognitive status are assessed at baseline, at the beginning of each treatment, at weeks 6 and 12, and then at 6, 9, 12, 16, 24 , 36, 48, and 60 months. PROJECTED ACCRUAL: A total of 238 patients will be accrued for this protocol.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

DISEASE CHARACTERISTICS: * Diagnosis of cerebral metastases meeting the following criteria: * One to three presumed brain metastases * Metastases must be from a histologically confirmed extracerebral site (e.g., lung, breast, prostate) * Histologic confirmation may have been from the primary tumor site, from another metastatic site (e.g., osseous metastasis, adrenal metastasis), or from the metastatic brain lesion(s) * Each lesion must measure less than 3.0 cm by contrast MRI of the brain performed within the past 21 days * Lesions must not be within 5 mm of the optic chiasm or within the brainstem * Eligibility for treatment with gamma knife or linear accelerator-based radiosurgery confirmed by a radiation oncologist * No primary germ cell tumor, small cell carcinoma, or lymphoma * No leptomeningeal metastases * Hormone receptor status not specified PATIENT CHARACTERISTICS: * Male or female * Menopausal status not specified * ECOG performance status 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 the body * No known allergy to gadolinium PRIOR CONCURRENT THERAPY: * More than 7 days since prior and no concurrent chemotherapy * No prior cranial radiotherapy * No prior resection of cerebral metastases * Concurrent hormonal agents, steroids, and/or anticonvulsants allowed

Locations (64)

Arizona Oncology-Deer Valley Center

Phoenix, Arizona, United States

Arizona Oncology Services Foundation

Scottsdale, Arizona, United States

Memorial Medical Center

Modesto, California, United States

Kaiser Permanente - Division of Research - Oakland

Oakland, California, United States

St. Joseph Hospital Regional Cancer Center - Orange

Orange, California, United States

Outcomes

Primary Outcomes

Neurocognitive Progression as Measured by the Number of Participants With Cognitive Deterioration by 3 Months

The primary endpoint was cognitive deterioration (progression), defined as a decline of greater than 1 SD from baseline on at least 1 of 7 cognitive tests (all tests are standardized based on published norms and transformed so that higher values represent improved cognition) at the 3-month post-SRS evaluation. The number of participants who experienced cognitive deterioration by 3 months is reported for each arm below. For primary analysis of the 3-month cognitive deterioration endpoint, the Fisher exact 2-group binomial test was used to compare the proportion of evaluable patients with 3-month cognitive deterioration between the 2 groups.

Time frame: 3 months post radiosurgery

Secondary Outcomes

Number of Participants With Local and Distant Tumor Control up to 3 Months

Number of Participants with Local and Distant Tumor Control up to 3 months is defined as....

Time frame: Up to 3 months

Overall Quality of Life, as Measured by Mean Change From Baseline [3 Month]

Quality of Life was assessed using the Functional Assessment of Cancer Therapy-Brain, for which the range is from 0 to 200 and higher scores indicate better QOL. The Quality of Life (QOL) scores were transformed to a 0- to 100-point scale (with 100 being most favorable), in which a 10-point change was considered clinically significant. Intergroup changes in QOL scores were compared using a 2-sample t test.

Time frame: From Baseline to 3-Month Evaluation

Long-Term Neurocognitive Status (Long-Term Cognitive Status), as Measured by Percentage of Long-term Survivors With Cognitive Deterioration at 12 Months

Long-Term Neurocognitive Status \> To ascertain in patients with one to three brain metastases whether there is better long-term neurocognitive status in patients who receive SRS alone (Arm A) compared to patients who receive SRS combined with WBRT (Arm B). Long-term survival status is defined as evaluable patients who survived for at least 12 months and had at least one cognitive assessment on or after 365 days.

Time frame: From baseline to 12 months

Overall Survival

Overall survival, defined as the time from randomization until death due to any cause, was compared between the groups using stratified log-rank tests.

Time frame: Up to 5 years