Amino acid positron emission tomography (PET) is increasingly utilized in the clinical workup of patients with glioma. To better understand the PET characteristics of IDH-mutant glioma according to the 2021 WHO classification of CNS tumours, this retrospective study explored the association between amino acid PET and magnetic resonance imaging (MRI) characteristics in patients with newly diagnosed IDH-mutant glioma. Patients with histologically verified IDH-mutant glioma who underwent [18F]FET PET/CT scans without prior treatment were included. PET parameters (PET-positivity according to PET RANO 1.0 criteria, maximal and mean tumour-to-background ratio (TBRmax, TBRmean), PET volume and uptake kinetics including minimal time-to-peak (TTPmin)) were assessed and compared with neuropathological findings and contrast-enhanced MRI including Dice similarity coefficients for spatial overlap between PET and MR signals. A total of 147 patients were included (79 astrocytomas, 68 oligodendrogliomas). Contrast enhancement was present in 44/147 tumours (29.9

Objective:Low grade glioma (LGG) is a disease associated with survival >10 years in most cases. Some patients, however, do not respond well to treatment and exhibit early progression as well as low overall survival. It is a challenge to identify these at-risk patients. Here, we used resting-state functional MRI (rsfMRI) to identify patients with LGG at risk for poor clinical outcome. Methods:Twenty-five patients with suspected LGG were prospectively enrolled. All patients underwent rsfMRI before any invasive procedure. Patient data was compared to a reference cohort of 1000 healthy controls to determine abnormality of functional connectivity on an individual level, resulting in a relative numerical measure called the dysconnectivity index (DCI). A median split was performed in order to divide the cohort into 2 groups with low and high DCI, respectively. Progression-free survival (PFS) as a primary outcome measure was calculated in both groups. Results:Twelve patients were diagnosed with astrocytoma, IDH-mutated, CNS WHO grade 2, and 13 patients were diagnosed with oligodendroglioma, IDH-mutated, 1p/19q-codeleted, CNS WHO grade 2. Eight patients had tumor progression, and 2 patients died during the observation period. 1/12 patients in the low DCI group and 7/13 patients in the high DCI group had tumor progression, resulting in significantly shorter PFS for patients with high DCI (P  = 0.028). No patient in the low DCI group died while 2 patients in the high DCI group died. Malignant transformation occurred in 4 patients with high DCI and in 0 patients with low DCI. There was no statistically significant difference in age, sex, diagnosis, and RANO resect class between the 2 groups. Conclusion:Greater disturbance of functional connectivity at the time of diagnosis as determined by rsfMRI was associated with shorter PFS in our cohort of patients with LGG. This suggests that rsfMRI might be used to identify LGG patients who are at risk of poor clinical outcome.

BACKGROUND:Assessment of postoperative tumor burden is essential in IDH-wildtype glioblastoma. The RANO resect classification stratifies patients based on residual tumor volume on postoperative MRI. [¹⁸F]FET PET can detect metabolically active tumor-suspicious tissue invisible on MRI. Its additional prognostic contribution remains ill-defined. METHODS:This retrospective bicentric study analyzed 140 patients with newly diagnosed IDH-wildtype glioblastoma and postoperative MRI and [¹⁸F]FET PET. MRI-derived residual tumor was classified by RANO resect; PET-derived volumes were defined using PET RANO 1.0 criteria. Spatial concordance was quantified using Dice coefficients. Prognostic associations were assessed by Cox regression. PET's incremental prognostic value was evaluated using a two-stage framework comparing MRI-only, PET-augmented, and fully adjusted models. RESULTS:Postoperative PET-defined volumes were substantially larger than MRI-defined volumes and showed minimal spatial overlap across RANO resect classes. PET-, T1CE-, and T2/FLAIR-based tumor volumes were independently associated with OS. Residual PET-volume was associated with increasing mortality risk and remained independently associated with OS (HR 1.021 per cm³, **p = 0.002). In an imaging-only model addition of PET improved time-dependent discrimination (ΔAUC(t) 0.03-0.07) and increased Harrell's C (ΔC ≈ 0.03), indicating improved prognostic discrimination. In the fully adjusted model, adding PET significantly improved model fit (*p = 0.0049), indicating prognostic information beyond MRI-derived tumor burden and clinical covariates. CONCLUSIONS:Postoperative PET visualized tumor-suspicious volume not identified by MRI and provided additional prognostic information. These findings support the potential role of PET for refined postoperative risk stratification, while prospective studies are needed to determine whether PET-informed postoperative management improves clinical outcomes.

Background and purpose:Brain metastases (BM) occur in up to 40% of patients with solid tumors. Following surgical resection, postoperative radiotherapy to the resection cavity is standard of care, yet optimal dose prescription and fractionation remain uncertain. This study evaluates clinical outcomes and toxicity of a standardized postoperative fractionated stereotactic radiotherapy (fSRT) regimen. Materials and methods:This retrospective single-center study included patients treated between 2017 and 2025 with postoperative fSRT for completely resected brain metastases. All patients received 25 Gy in five fractions, prescribed to the 80% isodose line. The planning target volume (PTV) was defined as the resection cavity plus a 2-mm margin. Primary endpoints were local control (LC) and symptomatic radiation necrosis. Secondary endpoints included overall survival (OS) and intracranial progression-free survival (iPFS). Survival outcomes were estimated using the Kaplan-Meier method, and Cox regression analyses were performed to identify prognostic factors. Results:A total of 159 patients and 181 resection cavities were analyzed. The median PTV was 22.3 cc, while the median clinical target volume (CTV) measured 13.8 cc. Median follow-up was 48 months. Local control rates at 12 and 48 months were 91.8% and 89.4%, respectively. Symptomatic radiation necrosis occurred in 3.2% of patients. Median OS was 31 months, and median iPFS was 20 months. In multivariable analysis, uncontrolled extracranial disease was the only independent predictor of inferior OS (hazard ratio 2.58, p < 0.001). Conclusion:Postoperative fSRT with 5 × 5 Gy prescribed to the 80% isodose line is safe, well-tolerated, and provides durable local control after surgical tumor removal. Additional evidence is eagerly anticipated from the ongoing phase 3 trials. Trial registration:The local ethical review committee of Ludwig-Maximilians-University Munich (application number: 24-0206) approved this study. The study has been officially registered on the German Clinical Trials Register (DRKS00034150) on December 20, 2024.

2075 Background: Amino acid PET is increasingly used to guide clinical decisions in glioma. For standardized response assessment, PET RANO 1.0 criteria have been formulated, but are primarily consensus-based and lack validation in molecular subgroups of diffuse gliomas. Methods: In this retrospective cohort study, patients with newly diagnosed or recurrent IDH -mutant glioma and at least two O-(2-[ 18 F]-fluoroethyl)-L-tyrosine ([ 18 F]FET) PET scans in 02/2013 - 08/2025 were included. PET was evaluated using PET RANO 1.0 criteria based on maximum and mean tumor-to-background ratios (TBR max /TBR mean ) and PET volume. Intervention-free survival (IFS) was used as endpoint. Results: Overall, 219 patients (110 [50.2%] oligodendroglioma, 106 [48.4%] astrocytoma, 3 with unknown 1p/19q status; 115 [52.5%] CNS WHO 2, 80 [36.5%] CNS WHO 3, 23 [10.5%] CNS WHO 4, 1 grading inconclusive) with 251 lesions were included. Median age at first PET was 45 years (range: 21-75), and 117 (53.4%) patients were male. In total, 220 treatment lines (173 [78.6%] first line treatment; 47 [21.4%] recurrence/progression) were followed, of which 135 (61.4%) involved radiotherapy and/or systemic treatment, and 85 (38.6%) observation. Median time between PET scans was 6.7 months (2.4-11.8). In first-line treatment at baseline, PET-based measurable disease was seen in 126/173 (72.8%), non-measurable in 38/173 (22.0%) and no measurable disease in 9/173 (5.2%). PET-based complete remission (PET-CR) was observed in 7/173 (4.0%), partial remission (PET-PR) in 32/173 (18.5%), stable disease (PET-SD) in 74/173 (42.8%), and progressive disease (PET-PD) in 60/173 (34.7%) patients. The primary driver of PET-PD was an increase in PET volume alone (27/60, 45.0%) or in combination with an increase in TBR max /TBR mean (19/60, 31.7%), followed by new measurable disease in 14/60 (23.3%) patients. In astrocytoma, IFS was shorter in patients with PET-PD (median: 10.0 months; 95%CI: 8.3-32.6) compared to PET-SD/-PR/-CR (33.0 months; 95%CI: 22.0-52.1; p = 0.043). Similar differences were seen in oligodendroglioma (PET-PD: 16.0 months; 95%CI: 11.7-63.3; vs. PET-SD/-PR/-CR: 34.5 months; 95%CI: 24.3-57.0; p = 0.036). At treatment for recurrence, baseline PET showed measurable disease in 37/47 (78.7%) and non-measurable disease in 10/47 (21.3%) patients. PET-CR was seen in 3/47 (6.4%), PET-PR in 16/47 (34.0%), PET-SD in 24/47 (51.1%) and PET-PD in 4/47 (8.5%) patients, with numerical differences in IFS (p = 0.16) according to PET response in recurrent disease. In both first-line treatment and recurrence, measurable disease at baseline was not associated with PET response (p > 0.05). Conclusions: Response assessment based on PET RANO 1.0 criteria is associated with outcome in IDH- mutant glioma. Further analyses considering MRI-based response assessment are ongoing for further validation of PET-based clinical trial endpoints.

2049 Background: In glioblastoma, precise visualization is a prerequisite for optimal resection strategies and accurate radiotherapy volume definition. In routine practice, contrast-enhanced MRI (CE-MRI) is most commonly used; however, it can underestimate tumor extent when viable tumor is present without blood–brain barrier disruption and therefore without contrast uptake. The present study examined whether amino acid PET with O-(2-[ 18 F]fluoroethyl)-L-tyrosine (FET) can better visualize the true distribution of tumor tissue and thereby improve preoperative assessment. Methods: In this prospective, biopsy-validated single-center study, in 61 patients with IDH-wildtype glioblastoma (44 newly diagnosed, 17 recurrent) 472 biopsies spatially correlated with preoperative FET PET and CE-MRI were histopathologically evaluated. Diagnostic metrics were calculated and compared between modalities using McNemar and Chi² tests (p = 0.05). Results: Overall, FET PET identified tumor tissue with significantly higher sensitivity than CE-MRI (91.2% vs. 55.7%; p < 0.001). When benchmarked against T2/FLAIR, FET remained more sensitive (85.3%; p = 0.012) while also demonstrating a pronounced gain in specificity (82.5% vs. 33.3%; p < 0.001). Remarkably, there was the high reliability of FET in regions without MRI contrast enhancement: biopsies taken from FET-positive areas without contrast enhancement showed a positive predictive value of 98.3%. Subgroup analyses consistently demonstrated the advantage of FET across clinical and histological strata, including newly diagnosed and recurrent disease (p < 0.001), as well as within cohorts with resection (p < 0.001; specificity p = 0.03) or biopsy (p < 0.001). Importantly, performance advantages were also observed regardless of histological tumor cell density, with FET exceeding CE-MRI in both histological strata (infiltration zone and solid tumor, both p < 0.001). Conclusions: FET PET demonstrated significant diagnostic superiority over CE-MRI for the visualization of glioblastoma tissue. Comparable positive predictive values in contrast-enhancing and non-enhancing regions indicate that FET PET detects tumor reliably, independent of the blood–brain barrier integrity. These findings support the integration of amino acid PET as an important component in target definition for both surgical and radiation planning in glioblastoma.

Clinical prognostication and decision-making in IDH-mutant glioma is increasingly complex, especially with new targeted treatment options like IDH-inhibitors. Individual patient risk stratification for better treatment planning is needed; however, standard prognostic models rely on clinical and histologic parameters as well as MRI, which may not fully reflect the tumor’s biological behavior. Positron emission tomography (PET) imaging of the 18 kDa translocator protein (TSPO) is known as surrogate marker of activated microglia and macrophages and enables non-invasive assessment of the tumor microenvironment and peri-/intratumoral inflammation as well as TSPO-positive tumor cells. The aim of this study was to investigate TSPO-PET imaging in IDH-mutant glioma and its association with outcome. In this monocentric, retrospective study, 46 patients with newly diagnosed IDH-mutant glioma who had undergone TSPO-PET imaging with [¹⁸F]GE180 prior to any therapeutic intervention were included. Quantitative PET parameters including mean and maximum standardized uptake values (SUVmax, SUVmean) and the respective PET-positive tumor volumes were evaluated for their association with clinical data and time to next intervention (TTNI), and overall survival (OS). The cohort consisted of 27 patients (58.7

Introduction:Stereotactic prepontine stenting (STS) has been shown to be a safe and effective alternative treatment to standard endoscopic third ventriculostomy (ETV) for the treatment of triventricular hydrocephalus (TVH). For ETV a success score (ETVSS) allows risk stratification for treatment failure, which was validated in young patients. For patients with TVH treated with STS a comparable success score was not performed to date. This was the reason why we wanted to test whether the ETVSS is also applicable to this patient cohort. Research question:Is the ETVSS also eligible for patients undergoing STS? Methods:TVH patients undergoing either ETV or STS between 2013 and 2024 were included retrospectively. Treatment failure was defined as absence of symptomatic and/or imaging improvement. ETVSS and its predicitive power were calculated for each group and correlated with outcome. Further statistical models were applied to create alternative scores. Results:50 STS patients had a mean ETVSS of 88.2 ± 3.9% compared to 81.8 ± 16.7% in 97 patients undergoing ETV (p = 0.009). Successful treatment was achieved in 87% of ETV and 96% of STS patients (p = 0.09). Mean ETVSS after successful treatment was 89.1 ± 2.9% versus 81.7 ± 4.1% with treatment failure in the STS and 84.1 ± 13.5% versus 71.7 ± 24.8% in the ETV group (p = 0.02 and p = 0.3). ROC analysis showed varied performance of ETVSS in the STS (AUC = 0.553) and ETV cohort (AUC = 0.766). Univariate analysis showed significant influence of the clivus-basilar artery diameter on treatment success in the ETV group. Identified risk factors did not allow the establishment of new scores. Conclusion:ETVSS did not enable prediction of treatment success by STS. Individual decision-making is essential, especially in patients with low ETVSS. Future studies must include a more heterogeneous patient population to enable new scoring systems specifically for patients undergoing STS.

Patients with glioblastoma represent a highly vulnerable cohort as they often experience rapid health deterioration with severe symptom burden including neurological, (neuro)psychological, and psychiatric symptoms. The aim of this sub-analysis of the “Early Palliative Care for Patients with Glioblastoma” (EPCOG) trial was to investigate the specific challenges of conducting a multicenter, randomized, controlled, clinical trial in glioblastoma patients testing a specialized palliative care (PC) intervention. We analyzed screening protocols and protocol deviations with respect to number and reasons for non-participation, skipped/delayed visits and attrition using descriptive statistics and content analysis of free-text comments. In total, 41.5

BACKGROUND:Positive effects of early integration of palliative care (EIPC) have been shown for systemic solid malignant tumors. We tested the hypothesis that EIPC improves quality of life (QoL), palliative care (PC) problems and mood in glioblastoma patients and reduces caregiver burden. METHODS:This randomized, rater-blinded, controlled trial conducted in six German university medical centers included glioblastoma patients within four weeks after diagnosis (first/recurrent) and their caregivers. Patients received standard care (control) or standard care and EIPC (intervention) for 12 months. Primary outcome was change in QoL after six months measured by the trial outcome index of the FACT-Br. Data were assessed 3-monthly for up to 24 months. RESULTS:Between 05/2019 and 04/2021 patients were enrolled and randomized to the intervention (n = 109) or control group (n = 108). QoL at month six was in favor of the intervention, however not statistically significant (mean difference 4.1 with 95% CI, -4.4 to 12.6, P = .34; intervention: n = 98 (m = 54/f = 44); control: n = 89 (m = 50/f = 39)). In an analysis adjusted for time of death, performed because of a significant survival difference (control superior to intervention, P = .018), QoL was better in the intervention group (P = .041). Secondary outcomes showed that patients significantly benefited from EIPC regarding PC problems and mood especially after intervention ended, while caregivers did not seem to benefit. CONCLUSIONS:Provided that the survival difference is included in the analysis, EIPC improves QoL in glioblastoma patients. This, in addition to improved mood and PC problems, demonstrates that EIPC sustainably improves 'how to live' but not 'length of life'.

Advanced breast cancer is associated with the development of brain metastases in 20%-40% of patients. Differential post-radiotherapy recurrence patterns depending on hormone receptor (HR) and human epidermal growth receptor 2 (HER2) status have been reported. We investigated recurrence patterns after microsurgical resection stratified for HR and HER2 expression. The institutional database was screened for patients who had undergone tumor resection for breast cancer brain metastases between 2013 and 2023. Patient and imaging data were analyzed. Response Assessment in Neuro-Oncology (RANO) guidelines were applied. Sixty-seven patients were identified. Nineteen patients (28%) were diagnosed with HR+/HER2-, 31 patients (46%) with HER2+, and 17 patients (25%) with triple-negative (TN) brain metastases. Local, i.e., in or adjacent to the resection cavity, or distant brain-specific progression-free survival (PFS) was shortest in patients with TN status, followed by patients with HER2+ and HR+/HER2- brain metastases (median: 170 vs. 419 vs. 1152 days; p < .01). Patients with HER2+ brain metastases showed earlier local progression than patients with HR+/HER2- status (HR 0.25; 95% CI 0.08-0.75; p = .01). The receptor status of the brain metastases diverged from the primary tumor in 13 patients (21%). In five patients (8%), a newly gained HR or HER2 expression was detected. Post-surgery recurrence patterns of breast cancer brain metastases are associated with the tumor biology. TN brain metastases show earliest local and distant recurrence, confirming the pressing need for better local and systemic treatments. As HER2+ brain metastases tend to recur locally, refinement of local strategies might be warranted.

Background ETERNITY was a retrospective and prospective cohort study investigating long-term (≥5 years) survival in patients with glioblastoma. We assessed the longitudinal course of neurocognitive function (NCF) and its determinants in a subgroup of patients with glioblastoma, IDH-wildtype, or astrocytoma, IDH-mutant, CNS WHO grade 4. Methods NCF was assessed at baseline and every 6 months using the Hopkins Verbal Learning Test-Revised, Controlled Oral Word Association Test, and Trail Making Test. Scores were converted to age-, sex-, and education-adjusted Z-scores and classified as impaired or unimpaired (Z ≤ -1.5). Linear mixed models were used to analyze NCF trajectories and associations with patient and tumor characteristics. Results At baseline (mean 9 years post-diagnosis, range 5-21 years), 145 of 185 patients (78%) were impaired on ≥1 test outcome. Impairment rates varied between 17.4% (HVLT-R delayed recognition) and 58.7% (TMT B). NCF remained largely stable over time, with a small decline in HVLT-R delayed memory. Left-sided and temporal tumor location were negatively associated with poorer NCF (p’s.01 to.03). Frontal tumor location was associated with higher psychomotor speed and cognitive flexibility (p’s <.001). Patients with IDH-mutant tumors performed worse on delayed recognition, whereas IDH mutation and MGMT promoter methylation were linked to improved phonemic fluency over time. Conclusions The majority of long-term survivors with astrocytoma, IDH-mutant, CNS WHO grade 4, and glioblastoma IDH-wildtype show neurocognitive impairment. Nonetheless, NCF is generally stable, with tumor location and molecular features associated with specific outcomes. These insights can help guide patient counseling and personalized care.

Background:Malignant gliomas are heterogeneous brain tumors with extensive neovascularization. Conventional gradient-echo dynamic susceptibility contrast (GRE-DSC) perfusion MRI may underestimate microvascular alterations. We hypothesized that a novel vascular model (NVM), based on Bayesian voxel-wise transit time distribution analysis, could yield higher perfusion metrics in untreated isocitrate dehydrogenase (IDH)-wild-type glioblastoma compared to standard vendor GRE-DSC algorithms. Methods:In this retrospective, single-center study, 89 patients with neuropathologically confirmed glioblastoma underwent pretherapeutic GRE-DSC perfusion MRI at 1.5 or 3.0 T. Perfusion maps were generated using both the NVM and default vendor algorithms. Using co-registered T1-post-contrast and T2/FLAIR images, two neuroradiologists independently assessed perfusion conspicuity of color-coded maps for each algorithm and manually performed region-of-interest analyses within visually identified tumor hotspots for quantification. Relative values of cerebral blood flow (rCBF), cerebral blood volume (rCBV), and mean transit time (rMTT) were normalized to contralateral normal-appearing white matter. Nonparametric tests evaluated group differences. Results:The NVM yielded enhanced hotspot delineation and significantly higher median normalized perfusion values than vendor algorithms (all P < .001), with excellent inter-rater reliability (Cohen's κ and intraclass correlation coefficients ≥0.86). At 3.0 T, NVM-derived rCBV was significantly higher than at 1.5 T (P = .008). Conclusions:NVM post-processing yielded higher normalized CBF, CBV, and MTT values within tumor hotspots than vendor pipelines, suggesting that Bayesian model-based perfusion analysis may enhance the detection of microvascular changes in glioblastoma. As validation against a gold standard is missing, prospective multicenter studies are warranted to confirm our findings, particularly with regard to treatment monitoring and clinical decision-making.

Ziel/Aim: Kürzlich wurden neue Response Kriterien unter Verwendung von Aminosäure-PET (PET RANO 1.0) eingeführt. Diese Studie analysiert erstmalig longitudinale [18F]FET-PET Daten von Patienten mit diffusem Gliom und wendet die neuen PET RANO 1.0 Kriterien an, um die PET-Charakteristika bei Baseline sowie Änderungen in den unterschiedlichen Response-Kategorien zu beschreiben.

Ziel/Aim: Patienten mit einem Glioblastom haben trotz multimodaler Therapie eine ungünstige Prognose. Die PET-Bildgebung wird zunehmend zur Charakterisierung und Therapieplanung bei Gliompatienten eingesetzt. In dieser Studie wird die Vorhersagegüte von Deep-Learning-Methoden mit der von Radiomics-basierten Methoden verglichen. Die zugrundeliegende Bildgebungsmodalität für den Vergleich sind FET-PET-Bilder.

Given the changing treatment landscape in IDH-mutant gliomas, prognostic stratification is pivotal to guide postoperative treatment decisions. Overall, 457 patients with IDH-mutant glioma and [18F]fluoroethyltyrosine or [11C]methionine positron emission tomography (PET) prior to radiotherapy or systemic treatment were included in this retrospective, bicentric study. Maximum and mean tumor-to-background ratios (TBRmax/TBRmean) and PET-positive volume (PET volume) were measured according to PET RANO 1.0 criteria, and their associations with time to next intervention (TTNI) and overall survival (OS) were evaluated. In total, 251 (54.9%) patients with astrocytoma and 206 (45.1%) with oligodendroglioma were included. In patients with astrocytoma undergoing PET before resection, measurable disease was associated with shorter TTNI compared to no/non-measurable disease (median 46.0 vs. 67.9 months; p=0.004). Univariable analysis showed an association of TTNI with TBRmax (Hazard ratio [HR]: 1.44 [95%CI: 1.23-1.68]), TBRmean (HR: 1.91 [95%CI: 1.34-2.71]) and PET volume (HR: 1.16 [95%CI: 1.07-1.26] per 10 mL increase). Multivariable analysis in astrocytoma adjusting for clinical factors such as age, WHO grade, extent in magnetic resonance imaging (MRI), extent of resection, and postoperative treatment confirmed the findings for TBRmax (HR 1.48 [95%CI: 1.09-2.01]) alongside T2/FLAIR extent (HR 1.03 [95%CI: 1.02-1.05] per 1 cm2 increase of product of maximum perpendicular diameters). In univariable OS analysis in astrocytoma, an association with TBRmax (HR: 1.40 [95%CI: 1.13-1.74]), TBRmean (HR: 1.97 [95%CI: 1.21-3.22]), and PET volume (HR: 1.23 [95%CI: 1.10-1.37]) was observed. Univariable TTNI analysis in oligodendroglioma showed an association with PET volume (HR: 1.11 [95%CI: 1.05-1.19]) which remained in multivariable analysis (HR 1.18 [95%CI: 1.03-1.36]). Further analyses considering timepoint of PET showed consistent results. In this retrospective analysis, associations of quantitative PET parameters with outcome were observed after adjusting for known prognostic factors. Prospective validation in clinical trials including PET imaging is needed to establish PET-based prognostic signatures.