Therapy monitoring of mTOR-inhibitors using 3D reconstruction of SEGA volume, DTI and SVS

Abstract

Objective: Subependymal giant cell astrocytomas (SEGAs) are WHO Grade I tumors, which occur in 5–10% of tuberous sclerosis complex (TSC) patients. Due to their location next to the foramen of Monroe, these tumors can lead to severe complications and to the risk of rapid neurological decline and death. Everolimus, a mTOR1-inhibitor, was approved in 2011 for the treatment of asymptomatic slowly growing SEGAs with risk of CSF – flow obstruction or inoperable SEGAs. However, the response is variable, and cessation of treatment is often associated with rapid tumor regrowth, necessitating life-long treatment, associated with unknown long-term toxicity. Advanced data on in vivo tumor behaviour utilizing state-of-the-art imaging methods, such as 3D reconstructed volumetry, DTI, and MRSI, do not yet exist. Our aim is to provide insight into growth patterns of these tumors. Methods: Between 2010 and 2016, 26 patients with SEGA had MRI scans at our center. 13 of these had treatment with mTOR-Inhibitors. Since 2015 we included Single-Voxel Spectroscopy and DTI to our MRI-protocol. SEGA volume was measured manually using the program ITK snap. Preliminary results: We analyzed 9 patients (4–19 years) with Everolimus treatment. Before treatment, the median SEGA volume was 707 mm³ (2372–71 mm³). After 12 months of therapy, SEGA volumes were reduced by median 40% (75–+38%). In 3 patients, treatment had to be stopped. In one of these patients the SEGA volume increased after cessation of treatment by 64%, in relation to the tumor volume under Everolimus treatment. The analysis of the entire patient group, the DTI and SVS are still ongoing. Conclusion: The 3D reconstruction of SEGA volume is a precise method to investigate the growth behavior of SEGA and the response to the therapy with Everolimus. However further research is required to predict tumor growth and treatment-response.