CTNI-09. DOSE ESCALATION FOR NEOADJUVANT STEREOTACTIC RADIOSURGERY FOR LARGE BRAIN METASTASES: PHASE I RESULTS

Abstract

Abstract BACKGROUND Surgical resection may be required for large and symptomatic brain metastases. Adjuvant radiotherapy or stereotactic radiosurgery (SRS) is needed to reduce local recurrence. Adjuvant radiosurgery has been associated with higher rates of leptomeningeal failure and radionecrosis. We conducted a phase I trial for brain metastases greater than 2 cm in size to determine the safety of preoperative SRS at escalating doses. METHODS Radiosurgery dose was escalated at 3 Gy increments starting with RTOG 90-05 dosing for 3 cohorts based on maximum tumor diameter: 18 Gy for >2-3 cm, 15 Gy for >3-4 cm, and 12 Gy >4-6 cm. Dose limiting toxicity (DLT) was defined as grade III or greater acute toxicity. Patients underwent surgical resection within 2 weeks and were followed with imaging and physical evaluations every 3 months. RESULTS For tumor size >2-3 cm, patients were enrolled up to the second dose level (21 Gy); for >3-4 cm and >4-6 cm cohorts the third dose level (21 Gy and 18 Gy, respectively) was reached. 35 patients were enrolled with 36 brain metastases treated with preoperative radiosurgery. There were 2 DLT (wound issues) in the >3-4 cm arm at the third dose level and 1 DLT (hemorrhage) in the >4-6 cm arm at the third dose level. The maximal tolerated SRS dose (MTD) for >-2-3 cm arm was not reached, for >3-4 cm arm was 18 Gy and for >4-6 cm arm was 18 Gy. With a median follow-up of 64 months, the 6- and 12-month local control rates were 88.8% and 79.1%, respectively. The 2-year rate of LMD was 0%. CONCLUSION This Phase I preoperative SRS dose escalation trial found a MTD for brain metastases greater than 3 and up to 6 cm in size. The phase II trial will be conducted at the maximum tolerated SRS doses.