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Purpose/Objective(s) Brain metastasis is a frequent cause of morbidity and mortality in stage IV cancer patients. Efforts to treat brain metastasis include surgical resection, whole brain radiation treatment (WBRT), and stereotactic radiosurgery (SRS). In contemporary times, SRS is deployed utilizing conformal, high dose radiation with rapid dose fall off to limit neurocognitive toxicity seen with WBRT. In the combined modality setting wherein surgical resection is required, post-operative SRS is utilized with excellent local control. However, several difficulties may arise from treatment in the post-operative setting. Changes to the tumor bed necessitating increased margin for uncertainty, increased treatment normal brain tissue, treatment in a hypoxic field may portend for less-than-ideal treatment. Therefore, pre-operative SRS is being explored due to potentially better-defined target, less target uncertainty, and reports of less radionecrosis and less leptomeningeal disease. Therefore, our group conducted a phase II clinical trial exploring the efficacy of the preoperative SRS approach in regard to local brain control, distant brain control, and overall survival. Materials/Methods A phase II institutional non-randomized clinical trial was initiated at UPMC Hillman Cancer Center enrolling patients with brain metastasis of any malignant histology. Lymphoma, leukemia, multiple myeloma, or germ cell tumors were excluded due to their radiosensitive nature. Patients were to receive SRS followed by surgical resection. Inclusion criteria included ≥18yo, KPS≥50 with a life expectancy of 12 weeks. Patients could have no more than four lesions measuring 1.5-4.0cm in size. Patients that had tumors Results A total of 24 patients were enrolled on study. One patient was deemed unresectable due to risk to the peri- rolandic location. Median number of brain metastasis treated was one (range 1-3). The most common treated histology was non-small cell lung carcinoma (NSCLC) (9). Median days from consult to SRS was 3.9 days. Median SRS dose and fraction was 16.5Gy [range: 15-24Gy] in a single fraction. The median number of surveillance MRIs performed was 6 [range 1-17]. Local brain control was 90%, 90%, and 74% at 6, 12, and 24 months. Distant brain control at 6, 12, and 24 months was 66%, 60%, and 54% respectively. Progression free survival (PFS) and overall survival (OS) at 6, 12, and 24 months were as followed [46%, 38%, 29%] and [66%, 58%, 50%] respectively. Conclusion Preoperative stereotactic radiosurgery appears to have excellent local control with a 6- and 12-month local control rates of 90%. Further study is warranted in the continued exploration of preoperative radiation therapy.

PURPOSE: To document the 5- and 10-year rates of late toxicity and vertebral compression fracture (VCF) in long-term survivors after stereotactic radiosurgery for spine metastases. METHODS AND MATERIALS: A retrospective review was performed on 562 patients treated with SRS for spine metastases between April 2001 and July 2011. Selecting those with at least 5-year survival after SRS, included were 43 patients who collectively underwent 84 treatments at 54 spine sites. Most were treated with single-fraction stereotactic radiosurgery to a median dose of 16 Gy (range, 12-24 Gy), and 56% of sites had received prior external beam radiation therapy. Late toxicities and VCFs occurring in the absence of tumor progression were recorded. Binary logistic regression was used to identify predictors of late complications. RESULTS: Nine patients (17% of treatment sites) developed grade ≥2 late toxicities at a median time of 12.8 months (range, 4.2-59.0 months). Actuarial 5- and 10-year rates of grade ≥2 late toxicity were 17% and 17%, respectively. On multivariate analysis, only cumulative biologically effective dose (BED(3)) > 200 Gy (or EQD2(2Gy) [2-Gy equivalent dose calculated using an α/β ratio of 2] > 130 Gy) was associated with grade ≥2 late toxicity (P = .036). Maximum point BED(3) > 110 Gy (or EQD2(2Gy) > 70 Gy) to spinal cord or cauda equina was associated with grade ≥2 late neuropathy (P = .017). Nine VCFs (18%) occurred at a median time of 10.2 months (range, 3.2-57.2 months), with 5- and 10-year VCF rates of 17% and 17%, respectively. CONCLUSION: Stereotactic radiosurgery for primary treatment and reirradiation of spinal metastases is associated with a moderate risk of late toxicity with 10-year follow-up. Risk of late toxicity significantly increases with cumulative BED(3) > 200 Gy and spinal cord or cauda equina point BED(3) > 110 Gy. Patients remain at moderate risk of VCF up to 5 years after treatment, with a plateau in incidence thereafter up to 10 years.

BACKGROUND: Historically, survival for even highly select cohorts of brain metastasis patients selected for SRS alone is