Preop fSRS for Resectable Brain Metastases

The purpose of the study is to determine whether treatment with pre-operative hypofractionated stereotactic radiosurgery followed by surgery will improve time to local failure (TTLF) compared to the current standard of care.


Eligibility Criteria:
Inclusion Criteria:

* Histologically confirmed solid tumor malignancy other than lymphoma, or germ cell tumor. Brain biopsy is not required unless diagnosis is judged to be in doubt by the treating physician.
* Life expectancy must be deemed to be 3 months or more by a neurosurgeon, radiation oncologist, or medical oncologist with expertise in the treatment of metastatic cancer to the brain.
* Participants must have MRI evidence of \>/=1 brain metastasis no less than 10 mm and no greater than 60 mm in maximum diameter, deemed surgically resectable by neurosurgeon, not previously treated with Stereotactic Radiosurgery (SRS) or appropriate for fSRS.
* Each non-index lesion must be \</= 4.0 cm in maximal extent on contrasted MRI scan, and not otherwise require resection. The number of non-index lesions allowed will be at the treating physician's discretion, providing the use of whole brain radiotherapy is not used for treatment of these lesions.
* Participants must be either asymptomatic from their brain metastases or have symptoms which are well controlled with steroid medication.
* Systemic therapy such as immunotherapy, targeted therapy, or chemotherapy are permitted at treating physician's discretion.
* Karnofsky Performance Status (KPS) \>/=60.
* This study permits the re-enrollment of participant who has discontinued the study due to pre-treatment failure (i.e., the participant has not been treated). If re-enrolled, participant must be re-consented.
* Women of Childbearing Potential (WOCBP) must have a negative serum or urine pregnancy test within 7 days prior to the start of radiation therapy.
* Azoospermic males and WOCBP whoa re continuously not heterosexually active are exempt from contraceptive requirements. However, they must still undergo pregnancy testing as described.
* Investigators shall counsel WOCBP and male participants who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators shall advise on the use of highly effective methods of contraception (detailed in protocol), which have a failure rate of \<1% when used consistently and correctly.

Exclusion Criteria:

* Participants who have germ cell tumors, primary brain tumor, or lymphoma
* Participants with symptoms related to brain metastases not able to be controlled with steroids.
* Women who are pregnant or breastfeeding
* Women of childbearing potential who are not using an effective method of contraception
* Participants deemed medically unfit to undergo surgical resection of brain metastasis by the treating neurosurgeon because of medical comorbidities, such as those who are neurologically or hemodynamically unstable despite appropriate medical interventions.
* Participants who have had whole brain radiation within the previous three months.
* Any prior cranial radiotherapy targeting the index lesion
* Index lesion located in the brainstem
* Any participants with the following imaging findings:

Widespread definitive leptomeningeal metastasis Infratentorial mass effect with fourth ventricle effacement or hydrocephalus Supratentorial mass effect with greater than 10 mm of midline shift or hydrocephalus.

A brain metastasis that is located within 2 mm of the optic chiasm

* Active or prior: documented inherited hypersensitivity syndromes, certain collagen vascular diseases, and certain autoimmune diseases. For example, any radiation hypersensitivity syndrome, including, but not limited to, Gorlin syndrome, multiple sclerosis, ataxia-telangiectasia, scleroderma, and systemic lupus erythematosus.
* Inability to complete MRI with contrast of the brain, or a known allergy to gadolinium
* Participants receiving cytotoxic chemotherapies 7 days prior to or concurrently with fSRS. Note: All other systemic therapies (i.e., molecularly targeted therapies) will be reviewed on a case-by-case basis by study PI to determine if appropriate for study treatment and documented within the research record or EMR.
* If participant's treatment plan respecting normal tissue tolerances using dose fractionation specified within the protocol cannot be achieved.
* Inability or unwillingness to return for all the required follow-up visits
* Prisoners or individuals who are involuntarily incarcerated
* Individuals who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness