A Phase II Study to Determine the Efficacy of Pre-Operative Stereotactic Radiosurgery Followed by Resection for Brain Metastasis.

Abstract

PURPOSE/OBJECTIVE(S)\nBrain 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.\n\n\nMATERIALS/METHODS\nA 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 < 3cm in size were required to be symptomatic to enroll on trial. Patients were subsequently selected to receive 15Gy, 18Gy, or 24Gy, based on tumor size. All patients proceeded to surgical resection within seven days of SRS. The primary endpoint was local control of ≥ 85% when compared to historical control rate of 60%.\n\n\nRESULTS\nA 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.\n\n\nCONCLUSION\nPreoperative 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.