Nikola Mikic's research while affiliated with Aarhus University Hospital and other places

... 35 Another RCT with 21 patients 36 evaluated the effect of intraventricular irrigation using the irrigation system IRRAflow, 37 using a dual-lumen catheter for automatised fluid exchange based on periodic irrigation and aspiration. 38 The study was terminated early, due to safety concerns, 36 as they found that the intervention group had a higher rate of catheter occlusion Cisternal irrigation overall compared with conventional treatment for subarachnoid haemorrhage [13][14][15][16][17][18][19][20][21][22] Mortality Open access (HR: 4.4, 95% CI 0.6 to 31.2, p=0.14). They did not find any statistically significant difference in mortality or functional outcome between the intervention and control group. ...

... Its feasibility has been demonstrated in two trials, OptimalTTF-1 and OptimalTTF-2 (Mikic et al 2021). A standard operating procedure for the SR surgery is described in great detail by Mikic et al (2022). ...

... In the most extreme case of neighboring arrays, all energy will be disposed in the scalp with no antitumor effect as shown in Figure 7C. 41 Furthermore, minor adjustments in the positioning of the electrode array are needed during treatment to avoid skin damage. These minor adjustments do not significantly affect the field distribution [40][41][42] as shown in Figure 7B, where rotating the transducer array stepwise from 0°C to 150°C with 30°C increments around its own axis does not significantly affect the field intensity. ...

... Intraoperative magnetic resonance imaging (MRI) depicts the extent of resection [5], but is very costly, time consuming and a single-time point method [6], [7]. 5-ALA based fluorescence [8], [9] reveals residual tumor clusters, but only in a subset of brain tumors, such as glioblastoma and CNS WHO grade 3 glioma. Neuronavigation provides guidance but loses accuracy during surgery due to brain shift [10], and has limited value for HBT versus NBT interface identification. ...

... Therefore, minimizing the thickness and conductivity of edema might be beneficial in improving AEF treatment outcomes. TTFields-enhancing techniques such as skull remodeling (Korshoej et al 2016, Mikic et al 2021 might help to compensate for the field strength loss caused by the peritumoral edema. Beyond the stifling effects of peritumoral edema on the efficacy of AEF, the edema has other clinically-relevant implications including promoting GBM cell infiltration (Ohmura et al 2023), which has been found to be associated with GBM recurrence/progression (Qin et al 2021). ...

... First, the skull, which has a lower electrical conductivity than the adjacent layers such as subcutaneous tissue and dura, attenuates the voltage reaching the deeper tissue. Simulation studies demonstrate increased intensity of electric fields inside brain tumors when strategic bone resections are performed to mitigate against the attenuation of TTFields intensity caused by the skull (31,44). Second, the brain is surrounded by cerebrospinal fluid (CSF), which is more conductive than the underlying gray matter, thereby creating a shunt effect that decreases the deposition of TTFields intensity into the brain parenchyma and intraparenchymal tumor (40). ...

... Recently, it was proposed to introduce holes at strategic positions in the skull (skull-remodeling surgery, SR-surgery) to facilitate current flow into the tumor, and thereby enhance the anti-neoplastic dose of TTFields focally in the region of interest (Korshoej et al., 2016). The principle has been described and analyzed in preclinical modeling studies Mikic and Korshoej, 2021) and the concept translated into a phase 1 clinical trial demonstrating safety in 15 patients with recurrent GBM (Korshoej et al., 2020). Furthermore, the trial indicated prolonged overall survival (15.5 months) relative to 6-11 months in comparable first recurrence GBM trial population (Taal et al., 2014) and showed that an average of 32% (range 25-59%) field enhancement could be obtained with an mean skull defect area of 10.5 cm 2 (range 7-48 cm 2 ). ...

... While surgical cytoreduction remains essential for tumor debulking, the potential benefts must be weighed against the risks of postoperative complications, especially in cases where bevacizumab therapy fails. [16] This underscores the need for a nuanced approach in selecting appropriate Ansstas and Tran [30] Wong et al. [31] Kirson et al. [32] Lazaridis et al. [33] Bokstein et al. [35] Song et al. [36] Korshoej et al. [38] Onken et al. [39] TR=Total resection, N/A=Not available, GBM=Glioblastoma multiforme, CI=Confidence interval, TMZ=Temozolomide, HR=Hazard ratio, BEV=Bevacizumab, CT=Computed tomography, CTR=chemotherapy, RCT=radiochemotherapy, RT=radiotherapy candidates for surgical procedures and optimizing the timing of adjunctive therapies to maximize therapeutic efficacy while minimizing risks. [17] The stratification of treatment approaches, as highlighted in studies focusing on age-based cohorts and performance ratings, points to the critical importance of patient-specific considerations. ...

... We found that SR-surgery combined with TTFields was not associated with serious adverse events related to the intervention, and adverse events observed could be attributed to medical therapy or TTField treatment alone. In addition, the trial further indicated a promising treatment efficacy with prolonged overall survival and progression-free survival compared to historical data from comparable patient cohorts [18]. ...

... Several studies have simulated the distribution of TTFields in the cranium (31,32), chest (33), and abdomen (34,35). Notably, bone tissue contained within these models consistently retained an electrical field intensity greater than 1 V/cm, which is considered the minimal threshold for in vivo efficacy (25,36). ...