**2.1. Study population**

Between December 2013 and August 2017, 30 patients with newly diagnosed and histologically verified supratentorial GBM were included into the study. All patients underwent gross total or subtotal microsurgical removal of the tumor. Patients with the evidence of recent hemorrhage on baseline magnetic resonance imaging (MRI) of the brain, metal implants, and concurrent severe, intercurrent illness were excluded from the study. The study was approved by the Ethics Committee of Cancer Research Oncology of Tomsk National Research Medical Center. All patients provided informed written consent before being included in the study.

exceeded the largest tumor diameter by at least 3 cm and increased proportionally to the tumor depth. The heating temperature was gradually increased, focusing on the patient's tolerability of the procedure in accordance with the protocol recommended by the device

**Figure 1.** The protocol for transcranial local radiofrequency hyperthermia combined with radiation therapy and

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The applied energy of the electromagnetic field was increased during seven sessions and was dependent on the patients' tolerance. In subsequent treatment sessions, the power did not increase. The duration of the treatment session ranged between 20 and 60 min and the absorbed power during one session was from 42 to over 324 kJ. To prevent thermal burns of the skin and subcutaneous tissue, the surface of the electrodes was cooled by circulating

Baseline contrast-enhanced magnetic resonance imaging (MRI) of the brain was required before starting concurrent thermochemoradiotherapy (TCRT). All patients underwent a detailed history and physical examination before treatment. Control blood and urine tests were performed every week of thermochemoradiotherapy. The neurological and neuro-oph-

Overall survival and time to tumor progression/recurrence are the most important criteria for the assessment of response to adjuvant therapy in patients with GBM. All patients were followed up in the outpatient clinic setting. To assess treatment outcomes, contrast-enhanced MRI was performed a month after completion of treatment, every 3 months in the first 2 years and every 6–12 months thereafter. All MR images were evaluated using Response Assessment in Neuro-oncology criteria, RANO [74]. In case of suspicion of tumor progression, an extraordinary MRI was performed. When a patient did not show up for a scheduled appointment,

Adverse effects of radiation therapy were evaluated using RTOG/EORTC Scoring Criteria (1995), and side effects of chemotherapy were assessed using the NCIC-CTC grading scale.

thalmic evaluations were performed before and after completion of treatment.

information on the patient's health status was requested in his family relatives.

Thermal damage to the skin was classified according to the depth of the lesion.

manufacturer [73].

chemotherapy with temozolomide.

deionized water at a temperature of 12–16°C.

**2.3. Patient surveillance and follow-up**
