**2.2. Study design and treatment**

This uncontrolled cohort study aimed to assess the tolerability and efficacy of concomitant transcranial local radiofrequency hyperthermia combined with radiotherapy and chemotherapy with temozolomide to treat newly diagnosed glioblastoma after surgical treatment. The IDH mutation status was determined using immunohistochemical staining with the antihuman IDH1 R132H. Methylation of O6-methylguanine-DNA methyltransferase (MGMT) was evaluated using a quantitative methyl-specific polymerase chain reaction in real time. To assess surgical outcomes, postoperative contrast-enhanced MRI of the brain was used.

External beam radiation therapy (2.0 Gy per fraction, 5 days per week to a total dose of 60 Gy) was delivered using Theratron Equinox device. Chemotherapy with temozolomide was administered at a dose of 200 mg/m<sup>2</sup> /day for 5 days for every 28-day cycle. The first course of chemotherapy was administered a week after starting radiation therapy. Patients received local hyperthermia beginning from the second week of administering external beam radiotherapy (**Figure 1**). Local hyperthermia was given two times a week for 60 min. The interval between local hyperthermia session and radiation therapy was 20–40 min.

Local hyperthermia was given using Celsius TCS system, which uses electromagnetic waves with a frequency of 13.56 MHz (radio waves) for energy transfer. The area of heating Concurrent Thermochemoradiotherapy in Glioblastoma Treatment: Preliminary Results http://dx.doi.org/10.5772/intechopen.76264 171

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

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 manufacturer [73].

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