Editorial for “Apparent Diffusion Coefficient as Imaging Biomarker for IDH Mutation, 1p19q Codeletion, and MGMT Promoter Methylation Status in Patients with Glioma”

OpenAlex İngilizce

Gliomas, originating in glial cells of neuroepithelial tissue in the brain parenchyma, are a major cause of death and include glioblastoma, which is the most frequent primary malignant tumor of the central nervous system (CNS).1 Definitive diagnosis is based on biopsy with molecular profiling, but a radiological diagnosis can be achieved with MR imaging, including both standard T1- and T2-weighted sequences, preferably including imaging following gadolinium administration.2, 3 Optimal treatment often involves surgical excision where possible, and for some tumor types, radiation therapy and/or chemotherapy. Although the currently applicable treatment options for high-grade glioma, which is based on surgical resection, radiation therapy, and chemotherapy, have expanded during the last couple of decades, the prognosis for patients remains poor, with the disease generally recurring.3, 4 The fifth edition of the 2021—WHO Classification of CNS Tumors (WHO CNS-5), is the latest version of the international standard for grading of CNS tumors.5 It represents significant changes that determine the role of molecular diagnosis and also adheres to histopathology and immunohistochemistry in CNS tumor classification.5 1p/19q co-deletion and isocitrate dehydrogenase (IDH) mutation are prominent molecular biomarkers of glioma with prognosis and clinical presentation that has led to the combined evaluation of these biomarkers in this newly revised classification, a better match for the prognostic features and therapeutic strategies of gliomas.5 Regarding the diagnosis by imaging techniques, biomarkers derived from conventional MR imaging are often nonspecific. Therefore, various advanced MRI methods may be performed to determine additional information such as the grade of the probable glioma. The advanced MR imaging of gliomas focuses on the pathological parameters of gliomas, including perfusion, permeability, microstructure, metabolism, and/or chemical composition.6, 7 Ma et al investigated apparent diffusion coefficient ratio (ADCratio) value as a preoperative diagnostic imaging biomarker in gliomas and concluded that ADCratio values enable the identification of 1p/19q co-deletion and IDH mutation status in IDH mutated glioma. In the design of the present study by Ma et al, there are IDH mutant/1p19q mutant, IDH mutant/1p19q intact, and IDH wild-type groups, and also in high-grade glioma, O(6)-methylguanine-DNA methyltransferase (MGMT) methylated and non-methylated groups.8 MGMT methylation was not examined in the low-grade gliomas, which is not unreasonable as the clinical impact of MGMT status on benefit from temozolomide or other alkylating agents has not been determined. Furthermore, MGMT methylation in low-grade gliomas is often significantly associated with IDH mutation and/or 1p/19q co-deletion and these are well-established prognostic factors for survival. It is worth noting that there was no mention of the MGMT methylation status assay used. It is important to know this as, while the optimal assay has not reached broad consensus internationally, the two most commonly used assays are supported by evidence coming from randomized trials.9 In terms of the ADC biomarker development, for a method that involves operator positioning of regions of interests on a slice selected by the operator, the intra-observer and inter-observer errors were remarkably high. It is questionable whether this could be repeated in the clinic. It is also unclear what the performance accuracy would be in test sets from other centers, with a point estimate on the receiver operating characteristic curve fixed beforehand. The point estimates derived from the study select specificity at the expense of sensitivity. For IDH mutation status, it is unclear whether using age alone could yield the same results—which would clearly be more straightforward. Perhaps for 1p/19q co-deletion, presence of calcification might also be a simpler strategy if had been explored. If the aim of the paper is to develop preoperative diagnostic molecular biomarkers for the clinic, development must continue in future studies. The data used for biomarker development are obtained from gliomas with a definitive diagnosis. In the clinic, we would not know definitively whether the lesion on an MRI scan is a glioma or not, a priori. Even if we did, gliomas not otherwise specified were also excluded. Thus, the population from which images are extracted and put into a pipeline for a diagnostic result may not resemble the sample used in this paper. Still, imaging scientists can learn from this methodology to develop exciting new radiogenomic tools. Arif K. Salihoğlu wishes to express his gratitude to his supervisor, Prof. Dr. Ahmet Ayar, for his unwavering support.