LAUSR

The study by Li and Liu answers to a frequent question regarding the prognosis of the glioblastoma, after neurosurgical resection and standard medical care. It is well-known that glioblastoma multiforme (GBM) has a high rate of recurrence, however until now, no biomarkers were identified to predict the recurrence of GBM. The authors found serum and neuroimaging biomarkers with a high sensitivity and specificity in the prediction of recurrence of GBM, giving the possibilities of a better choice of therapy, and a more accurate prognosis to patients and caregivers. According to the 2021 WHO Classification of Tumors of the Central Nervous System, glioblastoma is classified as an adult-type diffuse gliomas, since it is the third most frequent malignant brain tumors observed in the adults, and it is considered as a grade IV astrocytoma, based on natural history, regardless of the presence or not of isocitrate dehydrogenase (IDH) mutation (glioblastoma IDH-wildtype). Glioblastoma is classified as primary-GBM (identified de novo, more than 90% of cases) and secondary-GBM (less than 10% of cases), deriving from previously low grade gliomas (WHO grades II or III), although they are histologically indistinguishable. Based on IDH-mutation, it is classified also as IDH-wildtype (primary GBM) or IDH-mutant (secondary GBM). The latter has a longer median overall survival, indicative of a less aggressive behavior. GBM is classified as recurrent (or progressive), if it appears again, after the usual standard therapy. GBM is the most common malignant primary brain tumor consisting of 14.3% of all brain tumors and 49.1% of malignant tumors, with an incidence rate of 3.23 per 100 000 population. Incidence of glioblastoma increases with age, with a peak at the age of 75–84 years (median age at diagnosis: 65 years). It is more common in males (ratio 1.6:1), and its 5-year relative survival is 5%. The median survival for untreated glioblastoma is 8 months. Histologically, GBM is characterized by “anatomical heterogeneity,” with variable combination of cell anaplasia, cell proliferation, necrosis, tumor infiltration, microvascular proliferation, and vascular permeability. Beyond IDH, other well-known genes and pathways altered in GBM include: TERT (telomerase reverse transcriptase) promoter mutation, combined gain of entire chromosome 7 and loss of entire chromosome 10 [+7/ 10], EGFR gene (epidermal growth factor receptor, 7p12) amplification, 1p19q co-deletion, TP53 mutations, MGMT (methylated O-methylguanine–DNA methyltransferase) gene-promoter methylation status. Although the number of genes related to the occurrence of GBM is increasing, a huge effort has been made to identify potentially genes correlated with recurrence of GBM. In a recent study, the decreased expression of two genes, LHX5 (LIM Homeobox 5, 12q24.13) and TLX1 (T cell leukemia homeobox 1, 10q24.31), seems to be involved in GBM recurrence and could be used as potential biomarkers for identification of GBM recurrence. The standard treatment of primary GBM consist of maximal safe neurosurgical resection followed by concomitant daily temozolomide (75 mg/m/day) and radiotherapy (60 gray in 2-gray fractions over 6 weeks), further followed by adjuvant six cycles of maintenance temozolomide (increased to 150–200 mg/m/day 1–5 every 28 days). This protocol should be adapted, based on patients age, comorbidities and tumor location (e.g., brainstem). The primary goals of neurosurgical resection consist of maximal safe resection. It is wellknown that a more extensive surgical resection is associated with longer life expectancy, although even radical tumor resection is frequently not curative: most patients recur within 6 months, due to its high degree of invasiveness, and the presence of highly tumorigenic cells (GBM stem cells) from which recurrent-GBM is thought to derive. Typical recurrence of GBM occurs locally, usually within 2 cm from the original lesion, but distant relapses with contralateral involvement are also possible in up to 10.3% of cases, and treatment Commentary on Li Z, Liu W. Diagnostic performance of perfusion-weighted imaging combined with serum MMP-2 and -9 levels in tumor recurrence after postoperative concomitant chemoradiotherapy of glioblastoma. Received: 15 November 2022 Accepted: 16 November 2022