Identification of occult brain metastases amenable to stereotactic radiosurgery by motexafin gadolinium (MGd) based treatment planning MRI: Results of a phase II trial of MGd and whole brain radiotherapy (WBRT) with stereotactic radiosurgery (SRS)

Abstract

2037 Background: Motexafin gadolinium (MGd) is a novel anti-cancer agent that selectively localizes in tumors and is detectable by MRI. Previous studies of patients (pts) with brain metastases (BM) demonstrated the detection of occult lesions after MGd administration not visible with gadolinium MRI contrast. The purpose of this study was to evaluate if MRI scanning after MGd improves SRS treatment-planning and treatment outcome by identifying and better defining lesions that can be treated with the SRS boost. Methods: Pts with 1–4 BM (< 4 cm diameter, or, if multiple, < 3cm) received WBRT (37.5 Gy) and MGd, 5 mg/kg/day during weeks 2–3 of WBRT, plus MGd, 5 mg/kg prior to treatment planning MRI and prior to SRS (21 Gy for lesions = 2 cm, 18 Gy for lesions 2.1–3.0 cm, and 15 Gy for lesions 3.1–4.0 cm). MRI was obtained within 4 weeks prior to enrollment with standard contrast, and after WBRT for SRS treatment planning with MGd and standard contrast. Patients were followed for neurologic progression and survival. Results: 45 patients with either lung cancer (76%), breast cancer (11%), melanoma (7%), or other cancers (7%), a median age of 58 years (range 42–74), and a median of 2 BM (range 1–4) were evaluable. In 9 of 42 patients (21%) with MRI data available, the MGd-based treatment planning MRI demonstrated at least one occult lesion not visualized on the screening MRI. The MGd-based treatment planning MRI detected 1 occult lesion in 6 pts, 2 occult lesions in 1 patient, and 3 occult lesions in 2 patients. Median survival for evaluable pts is 10 months; median time to neurologic progression or radiologic progresssion is not reached at 15 months. Grade 3+ neurotoxicity was limited to 1 pt with tumor necrosis and 1 pt with motor weakness. Most common Grade 3+ adverse events were pneumonia (9%) and DVT (9%). Conclusions: MGd-based treatment planning MRI for SRS identified occult BM that are amenable to SRS and are undetected with standard gadolinium contrast agents in 21% of the pts enrolled in this phase II trial. Treatment with MGd, WBRT and SRS to all lesions visualized resulted in improved survival and local control compared with historical results. [Table: see text]