BackgroundThere is an increasing interest in local tumor ablative treatment modalities that induce immunogenic cell death and the generation of antitumor immune responses.MethodsWe 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.ResultsThere 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.ConclusionIntracavitary 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.
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.
INTRODUCTION: Laser Interstitial Thermal Therapy has been used to treat both recurrent brain metastases after SRS and radiation necrosis, with a good success rate. OBJECTIVE: to evaluate the predictive factors associated with local recurrence after LITT in patients with brain metastasis after use of SRS with signs of progressive disease. METHODOLOGY: Single institution retrospective study with consecutive patients presenting with progressive disease after SRS for brain metastasis. Clinical, demographic and volumetric data were acquired. The primary end point was local recurrence. RESULTS: 56 patients were included, comprising 76 lesions previously treated with SRS. Patients were radiologically classified as presenting with radiation necrosis (35.5%), recurrence (47.4%) or unspecific progression (17.1%). Breast (30.3%), melanoma (21.1%) and NSCLC (25%) were the most common tumor primary histology. Dural based lesions were present in 26.3%, complete ablation was achieved in 65.8%, local recurrence happened in 31.6%, with a mean PFS of 19.5 months (SD 1.7). NSCLC had the worst PFS time with 10.1 months (p=0.33). Patients presenting with radiologically suggestive recurrence disease had the shortest PFS (13 months, p=0.076). Lesions with less than 6cc had the longest PFS (17.2) when compared with lesions with volumes larger than 6cc (11.6 months) (p=0.42). Dural based lesions had shorter PFS when compared to non-dural based lesions (23.4 x 9.2 months, respectively) (p=0.01). Lesions that were completely ablated had a PFS of 24.7 months, in comparison with incomplete ablated lesions (8.7 months) (p<0.01). Multivariate proportional hazard regression analysis showed a HR of 2.4 for breast or NSCLC histology (p=0.09), 2.2 for dural based lesions (0.093) and 0.3 for completed ablated lesions (p=0.023). CONCLUSIONS: There is evidence that the primary tumor histology, brain metastasis relation with the dura-mater and the extension of the ablation (complete x incomplete) are the major factors impacting the local recurrence rate.
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