Please select the eligibility criteria that correspond to the clinical trial below.
Title: Efficacy of Post-Surgical Stereotactic Radiosurgery for Metastatic Brain Disease: A Randomized Trial
Brief Summary: This randomized phase III trial studies stereotactic radiosurgery to see how well it works compared to clinical observation after surgery in treating patients with brain metastases. Stereotactic radiosurgery, a type of radiation therapy, may be able to send x-rays directly to the tumor and cause less damage to normal tissue.


Options:
A: DISEASE CHARACTERISTICS:

* Diagnosis of brain metastases from a histologically confirmed primary or metastatic extracranial tumor, meeting 1 of the following criteria:

  * Stable systemic cancer for the last 3 months (achieved by surgery, radiotherapy, chemotherapy, or hormonal therapy), defined as absence of symptomatic or radiological progression
  * Asymptomatic synchronous primary tumor (treatable by surgery, radiotherapy, chemotherapy, or hormonal therapy)

    * No metastases outside the CNS
  * Unknown primary tumor
* Must have one to three brain lesions, confirmed by enhanced MRI prior to radiosurgery or surgery

  * No brain stem metastases
  * No leptomeningeal metastases
  * No brain metastases from small cell lung cancer, lymphoma, leukemia, myeloma, or germ cell tumors
* Patients planning to undergo radiosurgery must meet the following criteria:

  * Largest diameter ≤ 3.5 cm for single metastasis
  * Largest diameter ≤ 2.5 cm for multiple metastases
  * Stereotactic biopsy required if not extracranial tumor (unknown primary tumor) OR extracranial diagnosis made more than 4 years previously
* Prior neurosurgery patients must have undergone complete surgical resection
* No recurrent brain metastases after prior surgery and/or radiosurgery and/or brain radiotherapy

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* WHO 0-2 (may be assessed under steroid therapy)

Life expectancy

* Not specified

Hematopoietic

* Not specified

Hepatic

* Not specified

Renal

* Not specified

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* See Disease Characteristics
* No concurrent chemotherapy during whole brain radiotherapy

Endocrine therapy

* See Disease Characteristics

Radiotherapy

* See Disease Characteristics

Surgery

* See Disease Characteristics
B: Inclusion Criteria:

* Single presumed brain metastasis on contrast magnetic resonance imaging (MRI) scan within two weeks before commencement of treatment.
* Systemic cancer diagnosed histologically or cytologically synchronous with, or within 5 years of treatment of the presumed brain metastasis (other than non-melanoma skin cancer and cancer in-situ of the cervix, neither of which would be reasonably attributable as the primary site). Exception - melanoma diagnosed \> 5 years previously is allowable in view of the extremely variable natural history of melanoma.
* Age \>= 18 (no upper age limit).
* Considered suitable for both S and RS by the neurosurgeon and radiation oncologist (see exclusions).
* Patient must agree to adjuvant WBRT.
* RTOG RPA Class 1 or 2 (Karnofsky Performance Status \[KPS\] \>= 70 after adequate trial of corticosteroids).
* RPA Class 3 patients (KPS \< 70) eligible if it is considered that the poor performance status is due primarily to the solitary metastasis, aggressive local treatment of which may be expected to restore good performance status. This would ordinarily be associated with minimal systemic disease burden.
* Accessible for treatment and follow-up.
* Patient is infertile or is aware of the risk of becoming pregnant or fathering children and will use adequate contraception.
* Written informed consent

Exclusion Criteria:

* Previous history of brain metastasis(es)
* Surgery indicated to relieve life-threatening raised intracranial pressure or excision required for tissue diagnosis (no extra-cranial site to biopsy ie unknown primary). However, prior diagnostic (non-excisional) biopsy is allowable - it is acknowledged that the 50% probability of a repeat surgical procedure on subsequent randomisation would not be acceptable to many patients and clinicians.
* Surgery contraindicated by site (e.g. thalamus, brain stem) or medical co-morbidities.
* Leptomeningeal disease.
* Primary is small cell lung cancer, germ cell tumour, lymphoma, leukaemia or myeloma.
* Prior cranial RT (including RS).
* Patient is pregnant.
C: Pre-registration Inclusion Criteria:

1. Number of Brain Metastases - Four or fewer brain metastases (as defined on the pre-operative MRI or CT brain scan) and status post resection of one of the lesions.
2. Non-CNS Primary Site - Pathology from the resected brain metastasis must be consistent with a non-central nervous system primary site. Note: Patients with or without active disease outside the nervous system are eligible (including patients with unknown primaries), as long as the pathology from the brain is consistent with a non-central nervous system primary site.
3. Size of Metastases - Any unresected lesions must measure \< 3.0 cm in maximal extent on the contrasted MRI or CT brain scan obtained ≤ 35 days prior to pre-registration. The unresected lesions will be treated with SRS as outlined in the treatment section of the protocol. Note: The metastases size restriction does not apply to the resected brain metastasis; with resected brain metastases only surgical cavity size determines eligibility.
4. Size of Resection Cavity - Resection cavity must measure \<5.0 cm in maximal extent on the post-operative MRI or CT brain scan obtained ≤35 days prior to pre-registration.

   Note: It is permissible for the resection of a dominant brain metastasis to include a smaller "satellite" metastasis as long as the single resection cavity is less than the maximum size requirements.
5. Tumor Staging Procedures - All standard tumor-staging procedures necessary to define baseline extra cranial disease status completed ≤42 days prior to pre-registration.
6. Treatment with Gamma Knife or Radiosurgery - Able to be treated with either a gamma knife or a linear accelerator-based radiosurgery system.
7. Age ≥ 18 years
8. Neurocognitive Testing - Willing and able to complete neurocognitive testing without assistance from family and companions. Note: Because neurocognitive testing is one of the primary goals of this study, patients must be able to utilize English language booklets (and/or French booklets if enrolled in Canada).
9. Quality of Life (QOL) Questionnaires - Willing and able to complete QOL by themselves or with assistance
10. ECOG Performance Status - ECOG Performance Status (PS) 0, 1, or 2.
11. SRS Credentialed by IROC Houston Quality Assurance - The site's SRS facility is IROC Houston Quality Assurance approved.
12. Neurocognitive Testing Credentialing - The site study team member performing neurocognitive testing of patients must have credentialing confirming completion of the neurocognitive testing training of the protocol.
13. Written Informed Consent - Provide written informed consent
14. Mandatory Samples for Correlative Tests - Willing to provide mandatory blood and urine samples for correlative research purposes.

Pre-registration Exclusion Criteria:

1. Pregnancy, Nursing and Contraception - pregnant women, nursing women and men or women of childbearing potential who are unwilling to employ adequate contraception throughout the study and for men for up to 3 months after completing treatment.
2. Prior Cranial Radiation Therapy
3. MRI or CT Scans - Inability to complete a MRI or CT scan with contrast of the head.
4. Gadolinium Allergy - Known allergy to gadolinium.
5. Cytotoxic Chemotherapy - Planned cytotoxic chemotherapy during the SRS or WBRT.
6. Other Tumor Types - Primary germ cell tumor, small cell carcinoma, or lymphoma
7. Leptomeningeal Metastasis - Widespread definitive leptomeningeal metastasis
8. Location of Brain Metastasis - A brain metastasis that is located ≤ 5 mm of the optic chiasm or within the brainstem.

Randomization Inclusion Criteria:

1. Number of Unresected Lesions - Post-operative MRI or CT scan confirmed zero, one, two or three unresected lesions.

   1.1 Each unresected lesion must measure ≤ 3.0 cm in maximal extent on the contrasted post-operative MRI or CT brain scan.

   1.2 Note: The pre-registration, post-operative, brain scan may be used for the randomization scan if obtained ≤ 28 days prior to randomization.

   1.3 Note: If there are no unresected brain metastases (i.e., all brain metastases have been resected), a post-operative CT brain scan may be used if obtained ≤ 28 days prior to randomization.
2. Size of Resection Cavity - Post-operative MRI or CT scan confirms resection cavity measures \< 5.0 cm in maximal extent.

   2.1 Note: The pre-registration, post-operative brain scan may be used for the randomization scan if obtained ≤ 28 days prior to randomization.

   2.2 Note: If there are no unresected brain metastases (i.e., all brain metastases have been resected), a post-operative CT brain scan may be used if obtained ≤28 days prior to randomization.
3. Urine or Serum Pregnancy Test - Negative urine or serum pregnancy test done ≤ 7 days prior to randomization, for women of child bearing potential only.

Randomization Exclusion Criteria: none
D: Inclusion Criteria:

1. Patients must be older than 3 years of age (radiosurgical frames cannot be placed on children younger than age 3).
2. Patients must have 3 or fewer newly diagnosed metastatic lesions in the brain with a complete resection of at least one lesion as determined the study neuroradiologist.
3. The resection cavity must have a maximum diameter of less than or equal to 4cm. This criteria will be determined by the study radiologist.
4. Additional unresected brain metastases (up to 2) must have a maximum diameter of less than or equal to 3 cm.
5. Patients must be considered candidates for SRS within 30 days of surgical resection.
6. Patients must have a Karnofsky Performance Scores (KPS) of at least 70 at the first post operative visit. Patients under 18 years of age must have a Lansky Performance Score of of at least 70.
7. Patients must be able to undergo an MRI scan.
8. Patients must agree to randomization as documented by signing the Institutional Review Board (IRB) approved consent form.

Exclusion Criteria:

1. Patients who have received prior radiation therapy to the brain for any reason.
2. There is radiographic evidence of leptomeningeal disease prior to study entry.
3. The primary tumor is small-cell lung cancer, lymphoma, leukemia, or multiple myeloma.
4. For females, if they are pregnant or breast-feeding (The exclusion is made because gadolinium may be teratogenic in pregnancy).

Answer: D