FDOPA-PET-Guided Resection In Glioblastoma: Correlation of Pathological Results For a More Meaningful Target Over the Contrast-Enhanced Nodule.

Background: Glioblastoma (GBM), also known as grade 4 glioma IDH wildtype, is the most common primary brain tumor in adults, as classified by the latest WHO classification of central nervous system tumors. Despite aggressive treatment, the prognosis remains poor, with an average overall survival of around 15 months. Standard treatment typically involves surgery followed by concurrent chemotherapy and radiotherapy, known as the Stupp Protocol. However, GBM's infiltrative nature often leads to tumor recurrence beyond the contrast-enhancing nodule margins. Areas beyond these margins harbor a significant number of tumor cells, potentially explaining the high recurrence rates. The extent of resection of the contrast-enhanced nodule correlates directly with progression-free and overall survival in patients with high-grade gliomas. Recent studies suggest that extending resection beyond this target, such as resecting FLAIR hyperintense regions, can improve survival if it does not compromise the patient's functional outcome. Compared to FLAIR volumes, the areas identified on brain PET using amino acids (11C-MET, 18F-FET, or 18F-DOPA) are smaller but still extend beyond the contrast-enhanced nodule. This study aims to demonstrate that FDOPA-PET areas with high tumor-to-normal tissue ratio (TNR), located outside the contrast-enhanced nodule and without FLAIR hyperintensity, contain oncologically significant glial tumor cells that require resection. Methods and Materials: In 2023, a prospective study (ResPGlioma) was initiated, recruiting adult patients (>18 years) with newly diagnosed grade 4 glioma who underwent FDOPA-PET within one week of surgery. These images were coregistered using the Brain lab system with contrast-enhanced T1-weighted (CE-T1w) and FLAIR sequences from brain MRI performed within two weeks of surgery. To mitigate the issue of brain shift, areas with high metabolic activity outside the contrast-enhanced nodule were biopsied for histological investigation before resection and compared with other sampled regions. Results: For the first five recruited patients, five different sample types were analyzed: contrast-enhanced nodule (CEN), FLAIR+PET, PET-only, FLAIR-only, and areas with no MRI-detectable disease. Five quantitative variables were measured: neoplastic, infiltrative, normal/reactive components, percentage of necrosis, and mitotic activity. Samples from PET-only areas (c) showed a high neoplastic component, with an average of 22.8 mitoses per 10 high-power fields (HPF), higher than samples from FLAIR+PET (b) and FLAIR-only (d) areas. The normal/reactive component was significantly lower in PET-only samples (4) compared to FLAIR-only samples (29). Conclusion: These preliminary results suggest that areas with high TNR on PET using amino acids are significant targets for supramaximal resection. These regions are more oncologically relevant than hyperintense areas identified by FLAIR alone, indicating their potential as alternative targets for resection to improve patient outcomes from an anatomopathological perspective. Moreover, resecting the PET hyperintense area not only removes the more metabolically active tumor tissue but also preserves a greater portion of normal brain tissue. Further studies with a larger cohort are necessary to validate these findings.