RTHP-22. INFLAMMATORY RESPONSE AFTER MODIFIED NANOTHERM AND RADIOTHERAPY OF RECURRENT GLIOBLASTOMA

Abstract

BACKGROUND: There is increasing interest in local tumor ablative treatment modalities which induce immunogenic cell death and the generation of tumor specific immune responses. METHOD(S): We report the case of a 42-years old female with recurrent GBM who was treated with intratumoral thermotherapy using superparamagnetic iron-oxide nanoparticles (NanoTherm, MagForce GmbH, Munich, Germany; Fe 112 mg/ml) combined with external beam radiotherapy. After tumor resection, the wall of the remaining cavity was covered with nanoparticles using hydroxycellulose mesh and fibrin glue to create high local particle concentrations for subsequent heating in an alternating magnetic field. Postoperative FET-PET-CT showed enhanced metabolic activity at the margins of the resection cavity indicating residual tumor. The Patient underwent six 1-hour hyperthermia sessions and received concomitant radiotherapy at a dose of 39.6 Gy (5 x 1.8 Gy/wk). 14 weeks later, she developed new clinical symptoms. A CT scan showed a ring-enhancing lesion with extensive perifocal edema surrounding the resection cavity, suggestive of abscess formation. The patient underwent re-surgery and was treated with dexamethasone and antibiotics. Microbiological testing was negative. Histopathology revealed sustained necrosis and large amounts of iron-oxide nanoparticles without evidence for tumor activity. The cellular components consisted of granulocytes, MPO+ macrophages and siderophages with ingested nanoparticles. In addition, CD3+ T-cells, predominantly CD8+ T-cells were detected. Follow-up FET-PET-CT two months later revealed no signs of tumor progression and decreasing edema. CONCLUSION(S): This is the first report demonstrating that the combination of modified NanoTherm therapy with radiotherapy can induce a strong inflammatory reaction at the resection cavity mimicking abscess formation. We assume that large amounts of cellular debris are released in situ, which can serve as a source of tumor antigens to elicit host CD8+T-cell mediated adaptive immune responses against the tumor. Further investigations are necessary to decipher immune-related effects of modified NanoTherm therapy.