NRG-BN012, A Randomized Phase III Trial of Pre-Operative Compared to Post-Operative Stereotactic Radiosurgery in Patients with Resectable Brain Metastases

Inclusion Criteria

- Radiographic confirmation of 1-4 brain metastases, one of which requires resection,

as defined by magnetic resonance imaging (MRI) with contrast obtained within 14 days

prior to registration

- The maximum diameter of the lesion to be resected on the post-contrast MRI, as

measured on any orthogonal plane (axial, sagittal, coronal), must measure > 2.0

cm and < 5.0 cm.

- The maximum diameter of the lesions not to be resected must measure < 4.0 cm

- Known active or history of invasive non-central nervous system (CNS) primary cancer

based on documented pathologic diagnosis within the past 3 years

- All brain metastases must be located > 5 mm from the optic chiasm and outside the

brainstem

- Patient is able to medically tolerate surgery and SRS

- The lesion chosen for surgical therapy must be deemed an appropriate target for

safe, gross total resection by the treating surgeon

- History/physical examination within 14 days prior to registration

- Age >= 18

- Karnofsky performance status (KPS) >= 60 within 14 days prior to registration

- A negative urine or serum pregnancy test (in persons of childbearing potential)

within =< 14 days prior to registration. Childbearing potential is defined as any

person who has experienced menarche and who has not undergone surgical sterilization

(hysterectomy or bilateral oophorectomy) or who is not postmenopausal for at least

12 consecutive months

- Participants who are sexually active must agree to use medically acceptable forms of

contraception during treatment on this study to prevent pregnancy

- The patient or a legally authorized representative must provide study-specific

informed consent prior to study entry and, for patients treated in the United States

(U.S.), authorization permitting release of personal health information

Exclusion Criteria

- Prior cranial radiotherapy, including whole brain radiotherapy, or SRS to the

resection site

- Note: The index lesion to be resected cannot have been previously treated with

SRS (i.e. repeat radiosurgery to the same location/lesion is not allowed on

this protocol). Previous SRS to other lesions is allowed

- Evidence of leptomeningeal disease (LMD)

- Note: For the purposes of exclusion, LMD is a clinical diagnosis, defined as

positive cerebrospinal fluid (CSF) cytology and/or unequivocal radiologic or

clinical evidence of leptomeningeal involvement. Patients with leptomeningeal

symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be

considered to have LMD even in the absence of positive CSF cytology. In

contrast, an asymptomatic or minimally symptomatic patient with mild or

nonspecific leptomeningeal enhancement (MRI) would not be considered to have

LMD. In that patient, CSF sampling is not required to formally exclude LMD, but

can be performed at the investigator's discretion based on level of clinical

suspicion

- Any medical conditions which would make this protocol unreasonably hazardous,

including, but not limited to: contraindications to general endotracheal anesthesia;

intracranial surgery; and stereotactic radiosurgery

- Primary histology of germ cell tumor, small cell carcinoma or lymphoma

- More than one brain metastasis planned for resection

- Inability to undergo MRI with contrast

- Planned administration of cytotoxic chemotherapy or tyrosine/multi-kinase inhibitors

within the 3 days prior to, the day of, or within 3 days after the completion of SRS

- Note: chemotherapy and immunotherapy outside of this window are allowed