During a 9-month period, 50 patients with brain neoplasms, referred to the Neurosurgery and Neuroradiology Units of the “Santa Maria alle Scotte” Medical Center of Siena (Italy), agreed to participate in this study. Only 18 were considered eligible for the study, which had been previously approved by Local Ethical Committee. Participants were screened before the experiment by a multidisciplinary team, including neurologists, radiologists, and neurosurgeons. Inclusion criteria were as follows: (i) age between 18 and 80 years, (ii) valid written informed consent, (iii) strong clinical and radiological suspicion of primary GBM or MTX, and (iv) lesion site presumably reachable by noninvasive stimulation (i.e., cortico-subcortical location). The exclusion criteria were as follows: (i) lesions in deep WM, brain stem, cerebellum, or basal ganglia; (ii) multiple brain lesions; (iii) concomitant radiochemotherapy due to the effect of radiotherapy on tumor perfusion that could alter the assessment of tES effects; (iv) severe dilatation of ventricles; and (v) any health problem or other potential contraindications to undergo the MRI and experimental procedures. Patients were carefully informed about the safety of tES as well as about commonly reported adverse/side effects to ensure informed consent.

After the initial MRI session (Fig. 1A), manual segmentation of the brain tumor was performed in preparation for the tDCS-MRI session (Fig. 1B). Three patients developed health complications before the experimental intervention (thrombocytopenia, status epilepticus, and severe intracranial hypertension) and were excluded. Rapid worsening of clinical conditions led to urgent neurosurgical intervention (2 to 3 days after clinical MRI) in seven patients who were therefore excluded. Stimulation sessions were conducted in eight patients (mean age, 62.5; SD, 13 years; five males and three females; see Table 1): Six were diagnosed with primary GBM and two with MTX from lung cancer. Participants had concomitant neurological conditions: seizures (n = 2), focal neurological deficits (n = 3), symptoms and signs of endocranial hypertension (n = 2); cognitive impairment (n = 1). Some patients received corticosteroids, levetiracetam, and heparin (n = 3) during the study. Tumors were located in different brain regions: frontal lobe (n = 4; two left-sided), parietal lobe (n = 2; one left-sided), and temporal lobe (n = 2; one left-sided). Histological analyses of patients with MTX classified their lesions as MTX of adenocarcinoma (immunohistochemical patterns: patient 2: TTF1+, CK7+, CKPOOL±, P15+, GATA3; patient 7: CK7+; TTF1+; p63; CDX2; CK20). For histological data of patients with GBM, please refer to table S1.

F, female; L, left; M, male; R, right.

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