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

The mechanism of enhanced cytotoxicity can include the increase in intracellular accumulation of chemotherapeutic drugs, the inhibition of DNA repair, and S-phase cell cycle block, when cells are most sensitive to heat. In addition, LHT increases the production of free radi-

Based on clinical data demonstrating the synergistic antitumor effect of noninvasive radiofrequency hyperthermia used in combination with chemotherapy and radiotherapy for tumors from various sites and recurrent glioblastomas, the goal of the study was to evaluate the effectiveness and safety of LHT combined with concurrent chemoradiotherapy for newly diag-

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

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

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

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

between local hyperthermia session and radiation therapy was 20–40 min.

/day for 5 days for every 28-day cycle. The first course

cals and can reverse drug resistance [47, 49, 50].

170 Glioma - Contemporary Diagnostic and Therapeutic Approaches

nosed glioblastoma.

**2.1. Study population**

**2.2. Study design and treatment**

administered at a dose of 200 mg/m<sup>2</sup>

**2. Methods**

study.

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-ophthalmic evaluations were performed before and after completion of treatment.

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

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