Modulated Electro-hyperthermia in Integrative Cancer Treatment for Relapsed Malignant Glioblastoma and Astrocytoma- Retrospective Multicenter Controlled Study

Magnetic resonance imaging of glioblastoma

Magnetic resonance imaging of glioblastoma



The study aims to evaluate the safety and efficacy of modulated electrohyperthermia (mEHT) to treat relapsed malignant glioma and astrocytoma versus. The therapy may have a promising role in the treatment and palliation of relapsed GBM and AST.

Patients characteristics

149 Patients with histologically diagnosed with Glioblastoma (GBM) (n= 111) and Astrocytoma (n=38) relapsed after surgery, adjuvant RT and TMZ therapy and no second line therapy performed. Median age was 60 years for GBM (range 33-86 years) and 50 years (25-71 years) for AST group.


The study was performed with modulated electro-hyperthermia (mEHT). mEHT was used to obtain predefined heating with an electric field increasing the field power in an energy-controlled manner. The therapeutic temperature used in the mEHT treatment was estimated to range from 40°C to 42.5°C.
Preprocedural medication administered to all patients before each mEHT to avoid brain edema was 250 mL of glycerol 18% and dexamethasone 12 mg. The selected area was treated 3 times per week for 8 weeks.The first treatment was always performed applying 40 W for 20 minutes (48 kJ energy). Time was gradually raised from 20 to 60 minutes and the power was increased according to a step-up power protocol from 40 up to 150 W (540 kJ) over 2 weeks.


Tumor Response
At the 3-month follow-up period, the Astrocytoma (AST) patients of mEHT group showed 2 (9%) CR, 8 (36%) PR, and 6 (27%) SD. The overall positive response of AST (CR + PR + SD) was 72% after mEHT and is significantly higher than the 37% observed after best supportive care (BSC) (PR = 6% and SD = 31%). Also, the objective response (CR + PR) (45% vs 6%, P > .005) was significantly higher than that of the BSC group. Progressive disease (PD) was observed in 4 (18%) patients in mEHT and in 9 (56%) of BSC.
At the 3-month follow-up period, the GBM showed 1 (4%) CR, 6 (21%) PR, and SD 8 (29%), with an overall positive response of 54% in the mEHT group, and 13 PD (46%). The GBM treated with BSC had 2 (2%) CR, 2 (2%) PR, and 12 (14%) SD, whereas PD was observed in 62 (75%). Overall positive response of GBM treated with BCS was 19% significantly lower (P < .05) than that of mEHT group.Survival The median OS of AST was 16.5 months (range 3-120 months) and 16 months (range 3-156 months) in the BSC and mEHT groups, respectively (P = .0065). Survival rate of AST at the first and second year in the mEHT group was 77.3% and 40.9%, respectively. The 5-year OS of AST was 83% after mEHT versus 25% after BSC. The median OS for GBM was 14 months (range 2-108 months) after mEHT and 9 months (range 2-84 months) after BSC. We observed 4 long-term survivors in the AST and 2 in the GBM group. Two of the long survivors in the AST and 1 in the GBM group were treated by mEHT, with an OS of 156, 62, and 108 months, respectively. The long survivor of BSC group had a survival of 84 months. Most patients reported a better quality of life (evaluated by subjective responses as reported during follow-up visits) after mEHT. Six patients had an objective clinical response and therapeutic benefit by mEHT measured by decreased ECOG values from 3 to 1 in 2 (9%) AST and 2 (7%) GBM patients and from 3 to 0 in 2 (9%) AST patients. Safety
mEHT toxicity was mostly mild (grade 1). We observed in the entire mEHT group (28 GBM and 22 AST) 1 (2%) headache, 1 (2%) scalp burn, and 5 (10%) seizures. All patients who reported seizures had experienced this symptom from the beginning of the disease. Seizures were resolved with medication, including diazepam 10 mg in 100 mL of saline and levetiracetam in tablets without any further episodes. The small total number of adverse events (5%) in this study supports the strong safety profile of mEHT.
Cardiac evaluation was performed for all patients with electrocardiography and echocardiography before and after the cycle of mEHT. No significant variations were observed.


Recurrent gliomas (GBM and AST) may benefit from mEHT, a safe and effective integrative therapy. Both GBM and AST patients showed higher response rates after mEHT than those who received best supportive care. Together with local control, the OS was also significantly improved by mEHT compared with the conventional BSC palliation in recurrent glioma patients. This study shows that mEHT is safe and well tolerated for the management of recurrent gliomas, rarely resulting in mild pain, burns, or discomfort.

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Scientific article publishing date 12/10/2018

Immucura identifier BSC21_038EN