SURG-32. COMBINED INTRACAVITARY THERMOTHERAPY WITH IRON-OXIDE NANOPARTICLES AND RADIOTHERAPY AS A PROMISING TREATMENT MODALITY IN RECURRENT GBM

Abstract

BACKGROUND: Treatment options for glioblastoma patients (GBM) at the time of recurrence are still limited. METHODS: We report a series of six recurrent GBM patients (median age: 62.5 years, median time to first recurrence: 5.7 months, range 2.9 to 15.0) who were treated with intratumoral thermotherapy using superparamagnetic iron-oxide nanoparticles (NanoTherm®, MagForce AG, Munich, Germany) combined with external beam radiotherapy. After resection, tumor cavities were covered with nanoparticles using hydroxycellulose mesh and fibrin glue to create high local particle concentrations for subsequent heating in an alternating magnetic field (“NanoPaste” technology). Patients underwent six 1-hour hyperthermia sessions and received concomitant or sequential radiotherapy at a dose of 39.6 Gy (5 x 1.8 Gy/week). RESULTS: During the course of the disease, four patients developed a clinical deterioration (median EFS=3.1 months, range 2.0 to 4.5). In all cases, CT scans showed contrast-enhancing lesions with prominent edema surrounding the resection cavity. Patients underwent re-surgery and were treated with tapered doses of dexamethasone. Histopathology revealed sustained necrosis and large amounts of iron-oxide nanoparticles without evidence for tumor activity or bacterial infection. Immunohistochemistry showed upregulation of HSP70, a prominent infiltration of CD68+ myeloperoxidase-positive macrophages with ingested nanoparticles and an increase of CD3+ and CD8+ T-cells which were not detectable in the pre-therapeutic tumor tissue. In addition, flow cytometric analysis of intratumoral T-cells showed a shift towards a Th1 phenotype with increased intracellular ratio of INF-γ to IL-4. Follow-up CT and PETCT scans revealed no signs of tumor recurrence in 5 out of 6 cases, whereas one patient developed a definite tumor progress (median PFS=5.8 months, range 2.0 to 17.9). CONCLUSION: Local NanoTherm® treatment combined with radiotherapy can induce a persistent inflammatory reaction at the resection cavity which might lead to long-term stabilization of recurrent GBM patients. These results warrant further investigations in a prospective clinical trial.