RESUMEN

Glioblastoma multiforme (GBM) is the most common and malignant primary intracranial tumor, and has a median survival of only 10 to 14 months with only 3 to 5% of patients surviving more than three years. Recurrence (RGBM) is nearly universal, and further decreases the median survival to only five to seven months with optimal therapy. Tumor-treating fields (TTField) therapy is a novel treatment technique that has recently received CE and FDA approval for the treatment of RGBM, and is based on the principle that low intensity, intermediate frequency electric fields (100 to 300 kHz) may induce apoptosis in specific cell types. Our center was the first to apply TTField treatment to histologically proven GBM in a small pilot study of 20 individuals in 2004 and 2005, and four of those original 20 patients are still alive today. We report two cases of GBM and two cases of RGBM treated by TTField therapy, all in good health and no longer receiving any treatment more than seven years after initiating TTField therapy, with no clinical or radiological evidence of recurrence.

Asunto(s)

Neoplasias Encefálicas/mortalidad , Terapia por Estimulación Eléctrica , Glioblastoma/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Adulto , Anciano , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/terapia , Femenino , Glioblastoma/patología , Glioblastoma/terapia , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Proyectos Piloto , Pronóstico , Tasa de Supervivencia

RESUMEN

BACKGROUND: The present study explores the efficacy and toxicity of combining a new, non-toxic, cancer treatment modality, termed Tumor Treating Fields (TTFields), with chemotherapeutic treatment in-vitro, in-vivo and in a pilot clinical trial. METHODS: Cell proliferation in culture was studied in human breast carcinoma (MDA-MB-231) and human glioma (U-118) cell lines, exposed to TTFields, paclitaxel, doxorubicin, cyclophosphamide and dacarbazine (DTIC) separately and in combinations. In addition, we studied the effects of combining chemotherapy with TTFields in an animal tumor model and in a pilot clinical trial in recurrent and newly diagnosed GBM patients. RESULTS: The efficacy of TTFields-chemotherapy combination in-vitro was found to be additive with a tendency towards synergism for all drugs and cell lines tested (combination index

RESUMEN

We have recently shown that low intensity, intermediate frequency, electric fields inhibit by an anti-microtubule mechanism of action, cancerous cell growth in vitro. Using implanted electrodes, these fields were also shown to inhibit the growth of dermal tumors in mice. The present study extends these findings to additional cell lines [human breast carcinoma; MDA-MB-231, and human non-small-cell lung carcinoma (H1299)] and to animal tumor models (intradermal B16F1 melanoma and intracranial F-98 glioma) using external insulated electrodes. These findings led to the initiation of a pilot clinical trial of the effects of TTFields in 10 patients with recurrent glioblastoma (GBM). Median time to disease progression in these patients was 26.1 weeks and median overall survival was 62.2 weeks. These time to disease progression and OS values are more than double the reported medians of historical control patients. No device-related serious adverse events were seen after >70 months of cumulative treatment in all of the patients. The only device-related side effect seen was a mild to moderate contact dermatitis beneath the field delivering electrodes. We conclude that TTFields are a safe and effective new treatment modality which effectively slows down tumor growth in vitro, in vivo and, as demonstrated here, in human cancer patients.

Asunto(s)

Neoplasias Encefálicas/terapia , Terapia por Estimulación Eléctrica , Glioblastoma/terapia , Recurrencia Local de Neoplasia , Adulto , Animales , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Terapia por Estimulación Eléctrica/efectos adversos , Femenino , Glioblastoma/patología , Humanos , Ratones , Microelectrodos , Modelos Biológicos , Neoplasias Experimentales/terapia , Proyectos Piloto , Ratas , Ratas Endogámicas F344 , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Ensayos Antitumor por Modelo de Xenoinjerto

RESUMEN

BACKGROUND: For a number of years, FDG-PET was considered as a gold standard for the differential diagnosis of recurrent glioma and radionecrosis. Recently published papers have introduced a wealth of scepticism into this area. The aim of this work is to specify the added value of FDG PET, as compared to MRI, in terms of diagnostics of recurrent gliomas in the clinical setting of the PET Centre Prague. MATERIAL AND METHODS: MRI and FDG-PET were used to examine 29 patients for suspicious glioma recurrence, after 30 open neurosurgical operations or re-operations combined with chemo- and/or radiotherapy. The sensitivity, specificity and accuracy of both examinations were calculated with respect to their micromorphological findings (n = 28) or the clinical and radiological follow-up (n = 2). RESULTS: MRI detected 23/24 tumour recurrences (sensitivity = 95.8%) and FDG PET only 15 of these (sensitivity = 62.5%). MRI specified only 3/6 radionecrotic lesions (specificity = 50.0%), while FDG PET identified 5/6 (specificity = 83.3%). Overall accuracy was 26/30 (86.7%) for MRI and 20/30 (66.7%) for FDG PET. In the subgroup of MRI positive or equivocal findings (n = 29) FDG PET was clearly positive in 15 cases. High-grade glioma recurrence was subsequently confirmed in all of them. On the other hand negative or equivocal FDG PET was associated in 5/14 cases (35.7%) with radionecrosis, in 3/14 (21.4%) with low-grade glioma and in 6/14 (42.9%) with high-grade glioma. CONCLUSIONS: MRI is the method of choice for the detection of glioma recurrence but it is associated with a high rate of false positive results. FDG PET has significantly lower sensitivity; nevertheless it does help to specify MRI positive lesions. FDG PET positive lesions give a very high probability of high-grade glioma, but its equivocal and negative findings are of no clinical value.