Hypofractionated Stereotactic Radiosurgery before Surgery for the Treatment of Resectable Brain Metastases

Inclusion Criteria

• Participants must have signed and dated an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal patient care
• Participants must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study
• Patients with 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. Primary brain tumor or glioma is excluded
• Participants life expectancy must be deemed to be >= 3 months by a neurosurgeon, radiation oncologist, or medical oncologist with expertise in the treatment of metastatic cancer to the brain.
• Participants must have magnetic resonance imaging (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 SRS, and appropriate for fSRS
• Each non-index lesion must measure =< 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
• Patients 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 treatment physician’s discretion
• Karnofsky performance status (KPS) >= 60 * Eastern Cooperative Oncology Group (ECOG) to KPS conversion: ** ECOG 0 = KPS 90-100 ** ECOG 1 = KPS 70-80 ** ECOG 2 = KPS 50-60 ** ECOG 3 = KPS 30-40 ** ECOG 4 = KPS 10-20 ** ECOG 5 = KPS 0
• Patient re-enrollment: this study permits the re-enrollment of a participant who has discontinued the study due to pre-treatment failure (participant has not been treated). If re-enrolled, the participant must be re-consented
• Men and women >= 18 years of age
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L ore equivalent units of human chorionic gonadotropin [HCG]) within 7 days prior to the start of radiation therapy
• Women must not be breastfeeding
• Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, they must still undergo pregnancy testing as described in this section
• Azoospermic males are exempt from contraceptive requirements
• At a minimum, participants must agree to the use of one highly effective method of contraception as listed below: * Highly effective methods of contraception have a failure rate of < 1% when used consistently and correctly. WOCBP participants and female partners of male participants who are WOCBP are expected to use one of the highly effective methods of contraception listed below. Male participants must inform their female partners who are WOCBP of the contraceptive requirements of the protocol and are expected to adhere to using contraception with their partner. Contraception methods are as follows: ** Progesterone-only hormonal contraception associated with inhibition of ovulation ** Hormonal methods of contraception, including oral contraceptive pills containing combined estrogen/progesterone, vaginal rig, injectables, implants, and intrauterine devices (IUDs) such as Mirena ** Nonhormonal IUDs, such as ParaGuard ** Bilateral tubal occlusion ** Vasectomized partner with documented azoospermia 90 days after procedure (this is a highly effective birth control method provided that the partner is the sole sexual partner of the WOCBP trial participant and that the vasectomized partner has received medical assessment of the surgical success) ** Intrauterine hormone-releasing system (IUS) ** Complete abstinence *** Complete abstinence is defined as the complete avoidance of heterosexual intercourse *** It is not necessary to use any other method of contraception when complete abstinence is elected; *** Participants who chose complete abstinence must continue to have pregnancy tests *** Acceptable alternate methods of highly effective contraception must be discussed in the event that the participant chooses to forego complete abstinence *** The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant UNACCEPTABLE METHODS OF CONTRACEPTION * Periodic abstinence (calendar, symptothermal, post-ovulation methods) * Withdrawal (coitus interruptus) * Spermicide only * Lactation amenorrhea method (LAM)

Exclusion Criteria

• Participants who have germ cell tumors, primary brain tumor, or lymphoma are ineligible
• Patients 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 are excluded
• Patients 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
• Patients 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 patient 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 chias
• 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 a MRI with contrast of the brain, or a known allergy to gadolinium
• Any patients 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 principal investigator (PI) to determine if appropriate for study treatment and documented within the research record or electronic medical record (EMR)
• If the patient’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