preoperative srs/srt vs postoperative srs/srt for brain metastases

Conditions: Brain Metastases

Summary: this pilot study is a randomized, open-label, 2-arm active-controlled phase ii clinical trial conducted at a single study site (uams). subjects will be randomized to one of the 2 treatment arms and stratified by size of index lesion and number of brain metastases. the investigators will prospectively compare preoperative (neoadjuvant) srs/srt to postoperative (adjuvant) srs/srt in patients undergoing surgical resection for brain metastases. the investigators hypothesize that neoadjuvant srs/srt prior to surgical resection of brain metastases will result in improved freedom from central nervous system (cns) events when compared to adjuvant srs/srt after surgical resection.


Eligibility criteria:
inclusion criteria: * patients with prior histopathological diagnosis of cancer other than small cell lung cancer, lymphoma, and germ cell histologies. * mr imaging of the brain with findings strongly suggestive of metastatic tumor(s) as assessed by the radiologist. * seen by a neurosurgeon or radiation oncologist and judged to be appropriate for participation in this study, including the ability to tolerate both surgery and srs/srt, e.g., the ability to lie flat in a stereotactic soft head frame. * ecog ≤ 2 * 1-2 index lesion(s) appropriate for resection, not previously treated with srs/srt. index lesion(s) should be \> 2 cm and \< 5 cm in largest dimension, and require resection. alternatively, patients with a diagnosis of melanoma and a lesion \< 1.5cm in largest dimension may also be included. o all other brain lesions must be appropriate for srs/srt alone and treated according to physician preference. prior neurosurgery and/or prior srs/srt at a non-overlapping location are permitted at the discretion of the treating physician. - mri confirmed 1-10 lesions, 1-2 of which are the index lesions undergoing surgery. each non-index lesion (up to 10) must measure ≤ 3.0 cm in maximal extent on contrasted mri scan, and not otherwise require resection. * clinical indication and plan for stereotactic radiosurgery to all known brain lesions requiring treatment (≤ 10 metastases). * surgical resection able to be performed within 15 days of radiotherapy completion. * written informed consent obtained from subject, or a legally designated power of attorney and ability for subject to comply with the requirements of the study. * negative pregnancy test in women of childbearing potential (wocbp) within 30 days of radiation. wocbp is a female patient less than 50 years of age or who has menstruated within the last 12 months. * platelet count \> 80 k/cumm, hgb \> 7.5 gm/dl, inr \ 1.5 k/cumm exclusion criteria: * not a surgical candidate per neurosurgeon's discretion. * contraindication to general anesthesia. * not a radiosurgical candidate per radiation oncologist's discretion. * metastatic germ cell tumor, small cell carcinoma, leukemia, multiple myeloma or lymphoma or any primary brain tumor * ecog \> 2 * \< 3 months expected survival * radiologic documentation of hydrocephalus in addition to symptoms of hydrocephalus * radiographic or cytologic evidence of leptomeningeal disease. * imaging findings: * midline shift \> 6mm * \>10 lesions, one of which is the index lesion * largest lesion \> 5cm * pregnancy * known allergy to gadolinium, pacemaker, or other contraindication such as metal implant that is not safe for mri. patients with mri-compatible implants are eligible. * patients who have local recurrence of previously treated brain metastasis. * patients who have received prior wbrt. * inherited radiation hypersensitivity syndromes o ataxia telangiectasia, nijmegen breakage syndrome, fanconi anemia, dna ligase iv, mre 11 deficiency, scid, bloom's syndrome * collagen vascular diseases o active systemic lupus erythematous (sle), scleroderma, mixed connective tissue disorder, polymyositis or dermatomyositis, crest syndrome * cytotoxic chemotherapy within 7 days prior to srs/srt. o molecularly targeted therapies, including immune-modulatory drugs, can be given within 7 days of srs/srt at the discretion of the treating physician. * patients who received anti-vegf therapy within 6 weeks prior to enrollment, as there is increased risk of fatal brain hemorrhage with surgical resection. * treatment plan respecting normal tissue tolerances using dose fractionation specified within the protocol cannot be achieved.