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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase III Randomized Trial of the Role of Whole Brain Radiation Therapy in Addition to Radiosurgery in Patients With One to Three Cerebral Metastases

Conditions
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Breast Cancer, Cognitive/Functional Effects, Lung Cancer, Metastatic Cancer, Prostate Cancer

Intervention / Treatment
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* Radiation: radiation therapy
* Radiation: stereotactic radiosurgery


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I<br>Patients undergo stereotactic radiosurgery (SRS) | Radiation: stereotactic radiosurgery<br> <br> |
| Experimental: Arm II<br>Patients undergo SRS as in arm I. Within 14 days, patients then undergo whole-brain radiotherapy 5 days a week for 2.5 weeks. | Radiation: radiation therapy<br>* Patients undergo radiation therapy 5 days a week for 2.5 weeks<br>Radiation: stereotactic radiosurgery<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 3 months post radiosurgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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.... | 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. | 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. | 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. | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cognitive/functional effects, tumors metastatic to brain, stage IV breast cancer, stage IV prostate cancer, stage IV non-small cell lung cancer, male breast cancer, recurrent breast cancer, recurrent prostate cancer, recurrent non-small cell lung cancer