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.

Somatostatin receptor (SSTR)-targeted PET/CT provides valuable clinical insights beyond standard imaging in meningioma patients. Due to its excellent diagnostic capabilities and favorable logistics, the 18F-labeled SSTR-targeting peptide SiTATE is increasingly in demand. We aimed to validate a recently proposed standard uptake value (SUV) threshold for accurate meningioma delineation in a clinically diverse patient cohort, including complex anatomical locations and lesions with prior surgical intervention. Consecutive patients with known or suspected meningioma who underwent [18F]SiTATE PET/CT and contrast enhanced cerebral MRI were included. Lesions were semi-automatically segmented on PET images using an individualized minimal SUV (SUVmin) within a manually defined volume of interest. Correlative CT and MRI images were used to refine segmentations for each lesion, identifying the optimal lesion-specific SUVmin to accurately capture the true volume of the meningioma. All lesions were additionally segmented using the recently proposed threshold of 4.0, and resulting volumes were compared. 61 patients with 109 lesions were analyzed: 40 (37

BACKGROUND: Somatostatin receptor (SSTR)-targeted PET is valuable for meningioma imaging due to high SSTR expression. [18F]SiTATE, a novel tracer, is not only promising for imaging neuroendocrine tumors but also for meningiomas. Standardized delineation methods on [18F]SiTATE PET are lacking. This study correlates CT-based volumes with PET-based delineation approaches to identify a threshold for standardized [18F]SiTATE PET volume assessment. METHODS: Patients with well-delineated, extraosseous meningioma on CT (≥ 1mL) who underwent [18F]SiTATE PET/CT were included. Volumes were assessed on contrast-enhanced CT and correlated with PET-based delineation approaches: (I) fixed SUV threshold, (II) isocontour thresholding relative to SUVmax (SUV%), and thresholds relative to (III) bone marrow (SUVBM), (IV) parotid gland (SUVparotis) and (V) pituitary gland (SUVsella). RESULTS: 19 meningiomas in 17 PET/CT scans (16 patients) were included. A fixed SUV of 4.0 (r = 0.783, p < 0.001) showed good correlation with CT volumes without skewed distribution on Bland-Altman-Plot analysis. Using isocontour-based thresholds, 45% SUVmax (r = 0.496, p = 0.031) showed the highest concordance. Best reference-based approaches were achieved by 150% SUVBM (r = 0.859, p < 0.001), 250% SUVparotis (r = 0.460, p = 0.047) and 70% SUVsella (r = 0.819, p < 0.001). However, background-based approaches showed a trend towards overestimation of PET-volumes in larger meningiomas as assessed on Bland-Altman-Plot analyses. Uptake intensities of reference tissues (SUVBM, SUVparotis and SUVsella) were not inter-correlated (p > 0.05 each). CONCLUSION: A fixed SUV threshold of 4.0 showed strong agreement with CT-based volumes in well-delineated, extraosseous meningiomas which offers a simple, clinically applicable method without technical requirements. Reference tissue-based methods showed similar correlations but tended to overestimate volumes in larger lesions.

The study explores the potential of ChatGPT, an advanced large language model (LLM) by OpenAI, in educating patients about meningioma, a common type of brain tumor. While ChatGPT has generated significant debate regarding its utility and ethics, its growing popularity suggests that patients may increasingly use such tools for medical information. The study specifically examines how patients who have undergone radiation therapy for meningioma perceive the information generated by ChatGPT, integrating both patient feedback and clinical assessment. Eight meningioma-related questions on diagnosis, treatment options, and radiation therapy were posed to ChatGPT 4. A questionnaire with these responses and feedback items was developed to assess utility, accuracy, clarity, and alignment with patients’ experiences. Nine clinicians first rated each response’s relevance, correctness, and completeness on a five-point Likert scale. Subsequently, 28 patients with meningioma completed the questionnaire during their first follow-up visit (three months post–radiation therapy). Finally, the same questions were presented to three other large language models (ChatGPT 4o mini, Gemini Free, Gemini Advanced), and seven blinded clinicians rated each model’s responses before selecting the most accurate, eloquent, and comprehensive overall. The study cohort included 28 meningioma patients, mostly female, with a median age of 60 years. Most patients found the information clear, accurate, and reflective of their experiences, with 60

PET is increasingly used for target volume definition in the radiotherapy of glioblastoma, as endorsed by the 2023 ESTRO-EANO guidelines. In view of its growing adoption into clinical practice and upcoming PET-based multi-center trials, this paper aims to assist in overcoming common pitfalls of FET PET-based target delineation in glioblastoma.

Background:The PRIDE trial (NOA-28; ARO-2024-01; AG-NRO-06; NCT05871021) is designed to determine whether a dose escalation with 75.0 Gy in 30 fractions can enhance the median overall survival (OS) in patients with methylguanine methyltransferase (MGMT) promotor unmethylated glioblastoma compared to historical median OS rates, while being isotoxic to historical cohorts through the addition of concurrent bevacizumab (BEV). To ensure protocol-compliant irradiation planning with all study centers, a dummy run was planned and the plan quality was evaluated. Methods:A suitable patient case was selected and the computed tomography (CT), magnetic resonance imaging (MRI) and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) contours were made available. Participants at the various intended study sites performed radiation planning according to the PRIDE clinical trial protocol. The treatment plans and dose grids were uploaded as Digital Imaging and Communications in Medicine (DICOM) files to a cloud-based platform. Plan quality and protocol adherence were analyzed using a standardized checklist, scorecards and indices such as Dice Score (DSC) and Hausdorff Distance (HD). Results:Median DSC was 0.89, 0.90, 0.88 for PTV60, PTV60ex (planning target volume receiving 60.0 Gy for the standard and the experimental plan, respectively) and PTV75 (PTV receiving 75.0 Gy in the experimental plan), respectively. Median HD values were 17.0 mm, 13.9 mm and 12.1 mm, respectively. These differences were also evident in the volumes: The PTV60 had a volume range of 219.1-391.3 cc (median: 261.9 cc) for the standard plans, while the PTV75 volumes for the experimental plans ranged from 71.5-142.7 cc (median: 92.3 cc). The structures with the largest deviations in Dice score were the pituitary gland (median 0.37, range 0.00-0.69) and the right lacrimal gland (median 0.59, range 0.42-0.78). Conclusions:The deviations revealed the necessity of systematic trainings with appropriate feedback before the start of clinical trials in radiation oncology and the constant monitoring of protocol compliance throw-out the study. Trial registration:NCT05871021.

Background and purpose: The PRIDE trial (NOA-28; ARO-2022-12; NCT05871021) is scheduled to start recruitment in October 2023. Its primary objective is to enhance median overall survival (OS), compared to historical median OS rates, in patients with methylguanine methlyltransferase (MGMT) promotor unmethylated glioblastoma by incorporating isotoxic dose escalation to 75 Gy in 30 fractions. To achieve isotoxicity and counteract the elevated risk of radiation necrosis (RN) associated with dose-escalated regimens, the addition of protective concurrent bevacizumab (BEV) serves as an innovative approach. The current study aims to assess the dosimetric feasibility of the proposed concept. Materials and methods: A total of ten patients diagnosed with glioblastoma were included in this dosimetric analysis. Delineation of target volumes for the reference plans adhered to the ESTRO-EANO 2023 guideline. The experimental plans included an additional volume for the integrated boost. Additionally, the 60 Gy-volume was reduced by using a margin of 1.0 cm instead of 1.5 cm. To assess the risk of symptomatic RN, the Normal Tissue Complication Probability (NTCP) was calculated and compared between the reference and experimental plans. Results: Median NTCP of the reference plan (NTCPref) and of the experimental plan (NTCPex) were 0.24 (range 0.11–0.29) and 0.42 (range 0.18–0.54), respectively. NTCPex was a median of 1.77 (range 1.60–1.99) times as high as the NTXPref. In a logarithmic comparison, the risk of RN is enhanced by a factor of median 2.00 (range 1.66–2.35). The defined constraints for the organs at risk were feasible. Conclusion: When considering the potential protective effect of BEV, which we hypothesized might reduce the risk of RN by approximately two-fold, achieving isotoxicity with the proposed dose-escalated experimental plan for the PRIDE trial seems feasible.

4-repeat (4R) tauopathies are neurodegenerative diseases characterized by cerebral accumulation of 4R tau pathology. The most prominent 4R-tauopathies are progressive-supranuclear-palsy (PSP) and corticobasal-syndrome (CBS) characterized by tau accumulation in subcortical nuclei as well as cortical neuronal dysfunction, as shown by PET-assessed hypoperfusion and glucose hypometabolism. Yet, there is a spatial mismatch between subcortical tau deposition patterns and cortical neuronal dysfunction and it is unclear how these two pathological brain changes are interrelated. Here, we hypothesized that subcortical tau pathology induces diaschisis-like neuronal dysfunction in functionally connected cortical regions. We included 47 patients with clinically diagnosed PSP or CBS who underwent structural MRI and 18 F-PI-2620 tau-PET. PI-2620 PET was recorded using a dynamic one-shot, two-stop acquisition protocol, to determine an early 0.5-2.5min post-tracer-injection perfusion window for assessing cortical neuroinjury in 200 cortical ROIs of the Schaefer atlas, as well as a 20-40min post-tracer-injection window to determine 4R-tau load in 32 subcortical ROIs of the TIAN atlas. We determined tau epicenters as 10% of subcortical ROIs with highest tau-PET, and assessed the connectivity of tau epicenters to cortical ROIs using an age-matched 3T resting-state fMRI template derived from 69 healthy elderly. Using linear regression, we assessed whether i) higher subcortical tau-PET was associated with overall reduced cortical perfusion and ii) whether cortical hypoperfusion was observed preferentially in regions closely connected to subcortical tau epicenters. As hypothesized, higher subcortical tau-PET was associated with lower cortical perfusion (R=-0,37, p-value: <0,011, Fig.1). Using group-average tau-PET and perfusion-PET, we found that the seed-based connectivity pattern of subcortical tau epicenters predicted cortical perfusion patterns, where cortical regions that were more closely connected to the tau epicenter showed stronger hypoperfusion (R=-0,16, p-value: <0,023, Fig.2A). This association was also observed on the subject level, as indicated by overall negative b-values of the association between tau epicenter connectivity and cortical perfusion (one-sample t-test: t-value: -3,45, p-value: <0,001, Fig.3). In 4R-tauopathies subcortical tau-accumulation is associated with remote neuronal dysfunction in functionally connected cortical regions. This suggests that subcortical tau pathology may induce diaschisis-like cortical dysfunction, which may contribute to clinical disease manifestation and clinical heterogeneity.

Progressive supranuclear palsy (PSP) is a 4-repeat tauopathy movement disorder that can be imaged by the 18F-labeled tau PET tracer 2-(2-([18F]fluoro)pyridin-4-yl)-9H-pyrrolo[2,3-b:4,5-c']dipyridine (18F-PI-2620). The in vivo diagnosis is currently established on clinical grounds and supported by midbrain atrophy estimation in structural MRI. Here, we investigate whether 18F-PI-2620 tau PET has the potential to improve the imaging diagnosis of PSP. Methods: In this multicenter observational study, dynamic (0-60 min after injection) 18F-PI-2620 PET and structural MRI data for 36 patients with PSP, 22 with PSP-Richardson syndrome, and 14 with a clinical phenotype other than Richardson syndrome (i.e., variant PSP) were analyzed along with data for 10 age-matched healthy controls (HCs). The PET data underwent kinetic modeling, which resulted in distribution volume ratio (DVR) images. These and the MR images were visually assessed by 3 masked experts for typical PSP signs. Furthermore, established midbrain atrophy parameters were measured in structural MR images, and regional DVRs were measured in typical tau-in-PSP target regions in the PET data. Results: Visual assessments discriminated PSP patients and HCs with an accuracy of 63% for MRI and 80% for the combination of MRI and 18F-PI-2620 PET. As compared with patients of the PSP-Richardson syndrome subgroup, those of the variant PSP subgroup profited more in terms of sensitivity from the addition of the visual 18F-PI-2620 PET to the visual MRI information (35% vs. 22%). In quantitative image evaluation, midbrain-to-pons area ratio and globus pallidus DVRs discriminated best between the PSP patients and HCs, with sensitivities and specificities of 83% and 90%, respectively, for MRI and 94% and 100%, respectively, for the combination of MRI and 18F-PI-2620 PET. The gain of sensitivity by adding 18F-PI-2620 PET to MRI data was more marked in clinically less affected patients than in more affected patients (37% vs. 19% for visual, and 16% vs. 12% for quantitative image evaluation). Conclusion: These results provide evidence for an improved imaging-based PSP diagnosis by adding 18F-PI-2620 tau PET to structural MRI. This approach seems to be particularly promising at earlier disease stages and could be of value both for improving early clinical PSP diagnosis and for enriching PSP cohorts for trials of disease-modifying drugs.

Purpose Early after [ 18 F]PI-2620 PET tracer administration, perfusion imaging has potential for regional assessment of neuronal injury in neurodegenerative diseases. This is while standard late-phase [ 18 F]PI-2620 tau-PET is able to discriminate the 4-repeat tauopathies progressive supranuclear palsy and corticobasal syndrome (4RTs) from disease controls and healthy controls. Here, we investigated whether early-phase [ 18 F]PI-2620 PET has an additive value for biomarker based evaluation of 4RTs. Methods Seventy-eight patients with 4RTs (71 ± 7 years, 39 female), 79 patients with other neurodegenerative diseases (67 ± 12 years, 35 female) and twelve age-matched controls (69 ± 8 years, 8 female) underwent dynamic (0–60 min) [ 18 F]PI-2620 PET imaging. Regional perfusion (0.5–2.5 min p.i.) and tau load (20–40 min p.i.) were measured in 246 predefined brain regions [standardized-uptake-value ratios (SUVr), cerebellar reference]. Regional SUVr were compared between 4RTs and controls by an ANOVA including false-discovery-rate (FDR, p < 0.01) correction. Hypoperfusion in resulting 4RT target regions was evaluated at the patient level in all patients (mean value − 2SD threshold). Additionally, perfusion and tau pattern expression levels were explored regarding their potential discriminatory value of 4RTs against other neurodegenerative disorders, including validation in an independent external dataset ( n = 37), and correlated with clinical severity in 4RTs (PSP rating scale, MoCA, activities of daily living). Results Patients with 4RTs had significant hypoperfusion in 21/246 brain regions, most dominant in thalamus, caudate nucleus, and anterior cingulate cortex, fitting to the topology of the 4RT disease spectrum. However, single region hypoperfusion was not specific regarding the discrimination of patients with 4RTs against patients with other neurodegenerative diseases. In contrast, perfusion pattern expression showed promise for discrimination of patients with 4RTs from other neurodegenerative diseases (AUC: 0.850). Discrimination by the combined perfusion-tau pattern expression (AUC: 0.903) exceeded that of the sole tau pattern expression (AUC: 0.864) and the discriminatory power of the combined perfusion-tau pattern expression was replicated in the external dataset (AUC: 0.917). Perfusion but not tau pattern expression was associated with PSP rating scale ( R = 0.402; p = 0.0012) and activities of daily living ( R = − 0.431; p = 0.0005). Conclusion [ 18 F]PI-2620 perfusion imaging mirrors known topology of regional hypoperfusion in 4RTs. Single region hypoperfusion is not specific for 4RTs, but perfusion pattern expression may provide an additive value for the discrimination of 4RTs from other neurodegenerative diseases and correlates closer with clinical severity than tau pattern expression.

Purpose Early after [ 18 F]PI-2620 PET tracer administration, perfusion imaging has potential for regional assessment of neuronal injury in neurodegenerative diseases. This is while standard late-phase [ 18 F]PI-2620 tau-PET is able to discriminate 4-repeat tauopathies (4RTs) from disease controls and healthy controls. Here, we investigated whether early-phase [ 18 F]PI-2620 PET has an additive value for biomarker based evaluation of 4RTs. Methods Seventy-eight patients with 4RTs (71±7y, 39 female), 79 patients with other neurodegenerative diseases (67±12y, 35 female) and twelve age-matched controls (69±8y, 8 female) underwent dynamic (0-60 min) [ 18 F]PI-2620 PET imaging. Regional perfusion (0.5-2.5 min p.i.) and tau load (20-40 min p.i.) were measured in 246 predefined brain regions [standardized-uptake-value-ratios (SUVr), cerebellar reference]. Regional SUVr were compared between 4RTs and controls by an ANOVA including false-discovery-rate (FDR, p<0.01) correction. Hypoperfusion in resulting 4RT target regions was evaluated at the patient level in all patients (mean value-2SD threshold). Additionally, perfusion and tau pattern expression levels were tested for discrimination of 4RTs against other neurodegenerative disorders, including validation in an independent external dataset (n=37), and correlated with clinical severity in 4RTs (PSP rating scale, MoCA, activities of daily living). Results Patients with 4RTs had significant hypoperfusion in 21/246 brain regions, most dominant in thalamus, caudate nucleus, and anterior cingulate cortex, fitting to the topology of the 4RT disease spectrum. However, single region hypoperfusion was not specific regarding the discrimination of patients with 4RTs against patients with other neurodegenerative diseases. In contrast, perfusion pattern expression discriminated patients with 4RTs well from other neurodegenerative diseases (AUC: 0.850). Discrimination by the combined perfusion-tau pattern expression (AUC: 0.903) exceeded that of the sole tau pattern expression (AUC: 0.864) and the discriminatory power of the combined perfusion-tau pattern expression was validated in the external dataset (AUC: 0.917). Perfusion but not tau pattern expression was associated with PSP rating scale (R = 0.402; p = 0.0012) and activities of daily living (R = -0.431; p = 0.0005). Conclusion [ 18 F]PI-2620 perfusion imaging mirrors known topology of regional hypoperfusion in 4RTs. Single region hypoperfusion is not specific for 4RTs, but perfusion pattern expression provides an additive value for the discrimination of 4RTs from other neurodegenerative diseases and correlates closer with clinical severity than tau pattern expression.

The novel tau-PET tracer [ 18 F]PI-2620 detects the 3/4-repeat-(R)-tauopathy Alzheimer’s disease (AD) and the 4R-tauopathies corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP). We determined whether [ 18 F]PI-2620 binding characteristics deriving from non-invasive reference tissue modelling differentiate 3/4R- and 4R-tauopathies. Ten patients with a 3/4R tauopathy (AD continuum) and 29 patients with a 4R tauopathy (CBS, PSP) were evaluated. [ 18 F]PI-2620 PET scans were acquired 0-60 min p.i. and the distribution volume ratio (DVR) was calculated. [ 18 F]PI-2620-positive clusters (DVR ≥ 2.5 SD vs. 11 healthy controls) were evaluated by non-invasive kinetic modelling. R1 (delivery), k2 & k2a (efflux), DVR, 30-60 min standardized-uptake-value-ratios (SUVR 30-60 ) and the linear slope of post-perfusion phase SUVR (9-60 min p.i.) were compared between 3/4R- and 4R-tauopathies. Cortical clusters of 4R-tau cases indicated higher delivery (R1 SRTM : 0.92 ± 0.21 vs. 0.83 ± 0.10, p = 0.0007), higher efflux (k2 SRTM : 0.17/min ±0.21/min vs. 0.06/min ± 0.07/min, p < 0.0001), lower DVR (1.1 ± 0.1 vs. 1.4 ± 0.2, p < 0.0001), lower SUVR 30-60 (1.3 ± 0.2 vs. 1.8 ± 0.3, p < 0.0001) and flatter slopes of the post-perfusion phase (slope 9-60 : 0.006/min ± 0.007/min vs. 0.016/min ± 0.008/min, p < 0.0001) when compared to 3/4R-tau cases. [ 18 F]PI-2620 binding characteristics in cortical regions differentiate 3/4R- and 4R-tauopathies. Higher tracer clearance indicates less stable binding in 4R tauopathies when compared to 3/4R-tauopathies. Keywords Tau , PI-2620 , binding , affinity , kinetic modelling

The novel tau-PET tracer [18F]PI-2620 detects the 3/4-repeat-(R)-tauopathy Alzheimer’s disease (AD) and the 4R-tauopathies corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP). We determined whether [18F]PI-2620 binding characteristics deriving from non-invasive reference tissue modelling differentiate 3/4R- and 4R-tauopathies. Ten patients with a 3/4R tauopathy (AD continuum) and 29 patients with a 4R tauopathy (CBS, PSP) were evaluated. [18F]PI-2620 PET scans were acquired 0-60 min p.i. and the distribution volume ratio (DVR) was calculated. [18F]PI-2620-positive clusters (DVR ≥ 2.5 SD vs. 11 healthy controls) were evaluated by non-invasive kinetic modelling. R1 (delivery), k2 & k2a (efflux), DVR, 30-60 min standardized-uptake-value-ratios (SUVR30-60) and the linear slope of post-perfusion phase SUVR (9-60 min p.i.) were compared between 3/4R- and 4R-tauopathies. Cortical clusters of 4R-tau cases indicated higher delivery (R1SRTM: 0.92 ± 0.21 vs. 0.83 ± 0.10, p = 0.0007), higher efflux (k2SRTM: 0.17/min ±0.21/min vs. 0.06/min ± 0.07/min, p < 0.0001), lower DVR (1.1 ± 0.1 vs. 1.4 ± 0.2, p < 0.0001), lower SUVR30-60 (1.3 ± 0.2 vs. 1.8 ± 0.3, p < 0.0001) and flatter slopes of the post-perfusion phase (slope9-60: 0.006/min ± 0.007/min vs. 0.016/min ± 0.008/min, p < 0.0001) when compared to 3/4R-tau cases. [18F]PI-2620 binding characteristics in cortical regions differentiate 3/4R- and 4R-tauopathies. Higher tracer clearance indicates less stable binding in 4R tauopathies when compared to 3/4R-tauopathies.