Combined intracavitary thermotherapy with iron oxide nanoparticles and radiotherapy as local treatment modality in recurrent glioblastoma patients.

BACKGROUND: There is an increasing interest in local tumor ablative treatment modalities that induce immunogenic cell death and the generation of antitumor immune responses. METHODS: We report six recurrent glioblastoma patients who were treated with intracavitary thermotherapy after coating the resection cavity wall with superparamagnetic iron oxide nanoparticles ("NanoPaste" technique). Patients underwent six 1-h hyperthermia sessions in an alternating magnetic field and, if possible, received concurrent fractionated radiotherapy at a dose of 39.6 Gy. RESULTS: There were no major side effects during active treatment. However, after 2-5 months, patients developed increasing clinical symptoms. CT scans showed tumor flare reactions with prominent edema around nanoparticle deposits. Patients were treated with dexamethasone and, if necessary, underwent re-surgery to remove nanoparticles. Histopathology revealed sustained necrosis directly adjacent to aggregated nanoparticles without evidence for tumor activity. Immunohistochemistry showed upregulation of Caspase-3 and heat shock protein 70, prominent infiltration of macrophages with ingested nanoparticles and CD3+ T-cells. Flow cytometric analysis of freshly prepared tumor cell suspensions revealed increased intracellular ratios of IFN-γ to IL-4 in CD4+ and CD8+ memory T cells, and activation of tumor-associated myeloid cells and microglia with upregulation of HLA-DR and PD-L1. Two patients had long-lasting treatment responses > 23 months without receiving any further therapy. CONCLUSION: Intracavitary thermotherapy combined with radiotherapy can induce a prominent inflammatory reaction around the resection cavity which might trigger potent antitumor immune responses possibly leading to long-term stabilization of recurrent GBM patients. These results warrant further investigations in a prospective phase-I trial.

Efficacy of Carboplatin/Paclitaxel-Based Radiochemotherapy in Locally Advanced Squamous Cell Carcinoma of Head and Neck.

BACKGROUND: Cisplatin-based chemotherapy (CTX) is commonly used concurrently with radiotherapy for head and neck cancer. The value of CTX regimens other than cisplatin for locally advanced squamous cell carcinoma of head and neck (LASCCHN) has not been well established. Here we compare the outcome of patients treated with different platinum-based chemotherapy regimens. METHODS: Medical records from 104 patients with LASCCHN treated with radiochemotherapy (RCTX) between February 2013 and August 2016 were analyzed. RESULTS: All patients were treated with intensity-modulated radiation therapy (51 definitive, 53 postoperative). The median total dose was 66.6 Gy and the median fraction dose was 1.8 Gy. 81 (78%) patients were administered cisplatin CTX, 23 (22%) patients received carboplatin and paclitaxel (CarboTaxol). The rate of recurrence was 38% in patients treated with cisplatin and 30% in CarboTaxol-treated patients (p = 0.6). Regarding the CTX regimens, event-free survival (EFS) was 37 versus 30 months (p = 0.6) and overall survival (OS) was 35 versus 28 months (p = 0.5) in cisplatin group versus CarboTaxol group, respectively. Significantly higher grade 3/4 acute toxicity in terms of dysphagia was observed following cisplatin-based RCTX (p = 0.002). In multivariable analysis, females and patients with early primary tumors (T1-2) have longer EFS and OS, regardless the CTX regimen. CONCLUSIONS: Primary or adjuvant RCXT with CarboTaxol is a safe and effective treatment alternative for LASCCHN patients with contraindication to cisplatin-based RCTX.