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Katzendobler, Sophie; Do, Anna; Weller, Jonathan; Dorostkar, Mario M.; Albert, Nathalie L.; Forbrig, Robert; Niyazi, Maximilian; Egensperger, Rupert; Thon, Niklas; Tonn, Joerg Christian; Quach, Stefanie (2022): Diagnostic Yield and Complication Rate of Stereotactic Biopsies in Precision Medicine of Gliomas. Frontiers in Neurology, 13. ISSN 1664-2295

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Background: An integrated diagnosis consisting of histology and molecular markers is the basis of the current WHO classification system of gliomas. In patients with suspected newly diagnosed or recurrent glioma, stereotactic biopsy is an alternative in cases in which microsurgical resection is deemed to not be safely feasible or indicated. In this retrospective study, we aimed to analyze both the diagnostic yield and the safety of a standardized biopsy technique.

Material and Methods: The institutional database was screened for frame-based biopsy procedures (January 2016 until March 2021). Only patients with a suspected diagnosis of glioma based on imaging were included. All tumors were classified according to the current WHO grading system. The clinical parameters, procedural complications, histology, and molecular signature of the tissues obtained were assessed.

Results: Between January 2016 and March 2021, 1,214 patients underwent a stereotactic biopsy: 617 (50.8%) for a newly diagnosed lesion and 597 (49.2%) for a suspected recurrence. The median age was 56.9 years (range 5 months−94.4 years). Magnetic resonance imaging (MRI)-guidance was used in 99.3% of cases and additional positron emission tomography (PET)-guidance in 34.3% of cases. In total, stereotactic serial biopsy provided an integrated diagnosis in 96.3% of all procedures. The most frequent diagnoses were isocitrate dehydrogenase (IDH) wildtype glioblastoma (n = 596; 49.2%), oligodendroglioma grade 2 (n = 109; 9%), astrocytoma grade 3 (n = 108; 8.9%), oligodendroglioma grade 3 (n = 76; 6.3%), and astrocytoma grade 2 (n = 66; 5.4%). A detailed determination was successful for IDH 1/2 mutation in 99.4% of cases, for 1p/19q codeletion in 97.4% of cases, for TERT mutation in 98.9% of cases, and for MGMT promoter methylation in 99.1% of cases. Next-generation sequencing was evaluable in 64/67 (95.5%) of cases and DNA methylome analysis in 41/44 (93.2%) of cases. Thirteen (1.1%) cases showed glial tumors that could not be further specified. Seventy-three tumors were different non-glioma entities, e.g., of infectious or inflammatory nature. Seventy-five out of 597 suspected recurrences turned out to be post-therapeutic changes only. The rate of post-procedural complications with clinical symptoms of the Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher was 1.2% in overall patients and 2.6% in the subgroup of brainstem biopsies. There was no fatal outcome in the entire series.

Conclusion: Image-guided stereotactic serial biopsy enables obtaining reliable histopathological and molecular diagnoses with a very low complication rate even in tumors with critical localization. Thus, in patients not undergoing microsurgical resection, this is a valuable tool for precision medicine of patients with glioma.

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