Pre-operative dual-time-point [18F]FET PET differentiates CDKN2A/B loss and PIK3CA mutation status in adult-type diffuse glioma: a single-center prospective study.

PURPOSE: While [18F]FET PET plays a complementary role in glioma imaging, it needs to be more comprehensively understood for improved characterization of glioma prior to surgery given the evolving landscape of molecular neuropathology. Thus, we investigated the utility of pre-operative dual-time-point [18F]FET PET in correlation with next-generation sequencing (NGS) data in patients with adult-type diffuse glioma (ADG). METHODS: Adult patients who were suspected to have primary glioma were prospectively recruited between June 2021 and January 2024. They underwent pre-operative dual-time-point static PET/CT at 20 min (early) and 80 min (delay) after [18F]FET injection. Semi-quantitative parameters of the hottest lesion (SUVmax) of tumour and the hottest lesion-to-normal brain ratio (TBRmax) were assessed from each summed image. Furthermore, the percentage changes (△) of SUVmax and TBRmax between two images were calculated. Histopathology of glioma was determined according to the 2021 WHO classification and NGS data. RESULTS: This study investigated a dozen genes in 76 patients, of whom 51 had isocitrate dehydrogenase (IDH)-wild-type glioblastoma, 13 had IDH-mutant astrocytoma, and 12 had IDH-mutant oligodendroglioma. Every tumour was [18F]FET-avid having TBRmax more than 1.6. Patients with CDKN2A/B loss had significantly higher values of SUVmax (5.7 ± 1.6 vs. 4.7 ± 1.3, p = 0.004; 5.0 ± 1.4 vs. 4.4 ± 1.2, p = 0.026) and TBRmax (6.5 ± 1.8 vs. 5.1 ± 1.7, p = 0.001; 5.3 ± 1.5 vs. 4.3 ± 1.3, p = 0.004) in both scans than patients without CDKN2A/B loss, even after adjustment for age, MRI enhancement, tumor grade and type of pathology. Furthermore, patients with PIK3CA mutation (16.2 ± 11.8 vs. 6.7 ± 11.6, p = 0.007) had significantly higher △SUVmax than patients without PIK3CA mutation, even after adjustment for age, MRI enhancement, tumor grade, and type of pathology. CONCLUSION: Among the dozen genes investigated in this prospective study in patients with ADG, we found out that CDKN2A/B loss and PIK3CA mutation status could be differentiated by pre-operative dual-time-point [18F]FET PET/CT.

Prospective longitudinal analysis of imaging-based spatiotemporal tumor habitats in glioblastoma, IDH-wild type: implication in patient outcome using multiparametric physiologic MRI.

BACKGROUND: Physiologic MRI-based tumor habitat analysis has the potential to predict patient outcomes by identifying the spatiotemporal habitats of glioblastoma. This study aims to prospectively validate the cut-off for tumor progression obtained from tumor habitat analysis based on physiologic MRI in ascertaining time-to-progression (TTP) and the site of progression in glioblastoma patients following concurrent chemoradiotherapy (CCRT). METHODS: In this prospective study (ClinicalTrials.gov ID: NCT02613988), we will recruit patients with IDH-wild type glioblastoma who underwent CCRT and obtained immediate post-operative and three serial post-CCRT MRI scans within a three-month interval, conducted using diffusion-weighted imaging and dynamic susceptibility contrast imaging. Voxels from cerebral blood volume and apparent diffusion coefficient maps will be grouped using k-means clustering into three spatial habitats (hypervascular cellular, hypovascular cellular, and nonviable tissue). The spatiotemporal habitats of the tumor will be evaluated by comparing changes in each habitat between the serial MRI scans (post-operative and post-CCRT #1, #2, and #3). Associations between spatiotemporal habitats and TTP will be analyzed using cox proportional hazard modeling. The site of progression will be matched with spatiotemporal habitats. DISCUSSION: The perfusion- and diffusion-derived tumor habitat in glioblastoma is expected to stratify TTP and may serve as an early predictor for tumor progression in patients with IDH wild-type glioblastoma. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02613988.

Radiographic and neurological outcomes of Gamma Knife radiosurgery for lower cranial nerve schwannomas: a single-institution experience.

OBJECTIVE: Gamma Knife radiosurgery (GKRS) is widely used for treating small- to medium-sized or postoperative residual, recurrent lower cranial nerve schwannomas (LCNSs). This study aimed to evaluate the radiographic and neurological outcomes of GKRS for LCNS. METHODS: A total of 60 patients with 47 jugular foramen schwannomas (JFSs) and 13 hypoglossal nerve schwannomas (HNSs) who underwent GKRS were included. Dysphagia (40.4%) and hoarseness (23.4%) were the most common preexisting symptoms associated with JFS, whereas tongue deviation (53.8%) was prevalent in HNS. The median tumor volumes were 3.2 cm3 and 2.2 cm3 for JFSs and HNSs, respectively. The median marginal dose administered to the tumor was 13 Gy (range 12-15 Gy). The median follow-up duration was 52.8 months. RESULTS: Local tumor control was achieved in 91.5% of JFSs and 92.3% of HNSs. The preexisting neurological symptoms improved in 48.9% of patients with JFS and remained stable in 29.8%. However, 10 patients (21.3%) experienced exacerbation of symptoms associated with cranial nerves VII, VIII, IX, X, and XI. Among these, 3 patients (6.4%) exhibited persistent symptomatic deterioration. Patients with HNSs demonstrated a stable trajectory without symptom aggravation. Larger tumor volume and cystic portion were significantly associated with tumor progression (p = 0.017 and 0.003, respectively), and post-GKRS transient swelling was associated with neurological deterioration (p = 0.044). CONCLUSIONS: GKRS is an alternative treatment option for LCNS that reduces surgical morbidity and enhances tumor control. However, GKRS can potentially lead to neurological deterioration, necessitating extreme caution throughout the procedure, specifically for JFSs.

Rhabdomyosarcoma of the skull with EWSR1 fusion and ALK and cytokeratin expression: a case report.

Rhabdomyosarcoma (RMS) comprises of heterogeneous group of neoplasms that occasionally express epithelial markers on immunohistochemistry (IHC). We herein report the case of a patient who developed RMS of the skull with EWSR1 fusion and anaplastic lymphoma kinase (ALK) and cytokeratin expression as cytomorphologic features. A 40-year-old man presented with a mass in his forehead. Surgical resection was performed, during which intraoperative frozen specimens were obtained. Squash cytology showed scattered or clustered spindle and epithelioid cells. IHC revealed that the resected tumor cells were positive for desmin, MyoD1, cytokeratin AE1/ AE3, and ALK. Although EWSR1 rearrangement was identified on fluorescence in situ hybridization, ALK, and TFCP2 rearrangement were not noted. Despite providing adjuvant chemoradiation therapy, the patient died of tumor progression 10 months after diagnosis. We emphasize that a subset of RMS can express cytokeratin and show characteristic histomorphology, implying the need for specific molecular examination.

Mapping Tumor Habitats in IDH-Wild Type Glioblastoma: Integrating MR Imaging, Pathologic, and RNA Data from Ivy Glioblastoma Atlas Project.

BACKGROUND: To spatially validate intratumoral subregions (tumor habitat) using physiologic MRI on pathology of the isocitrate dehydrogenase (IDH)-wildtype whole-glioblastoma sample. METHODS: Data of 20 patients (168 slides) were obtained from the Ivy Glioblastoma Atlas Project. On MRI, tumor habitats were defined using voxel-wise clustering of apparent diffusion coefficient (ADC) and cerebral blood volume (CBV) maps for contrast-enhancing lesion (CEL) and non-enhancing lesion (NEL). On pathology slides, normalized areas of leading edge (LE), infiltrating tumor (IT), cellular tumor (CT), hypervascular lesion (CThypervascular), and perinecrotic lesion (CTperinecrotic) were obtained. Gross specimen was co-registered on MRI and correlation between pathology-MRI habitats was calculated. RNA sequencing of 67 samples was assessed using 4 Neftel subtypes and further correlated with pathology. RESULTS: Six tumor habitats were identified: hypervascular, hypovascular cellular, and hypovascular hypocellular habitats for CEL and NEL. CT was correlated with hypovascular cellular habitat in CEL (r= 0.238, p =.005). IT was correlated with hypovascular cellular habitat in NEL (r= 0.294, p =.017). CThypervascular was correlated with hypervascular habitat in NEL (r= 0.195, p = .023). CTperinecrotic was correlated with imaging necrosis (r= 0.199, p =.005). Astrocyte-like subtypes were correlated with IT (r= 0.256, p <.001), while mesenchymal-like subtypes were correlated with CTperinecrotic area (r= 0.246, p <.001). CONCLUSION: Pathologically matched tumor subregions were cellular tumor with hypovascular cellular habitat in CEL and infiltrative tumor with hypovascular cellular habitat in NEL. Identification of the most aggressive as well as infiltrative tumor portion can be achieved using non-invasive MRI tumor habitats.

Enhancing Prognostication and Treatment Response Evaluation in Primary CNS Lymphoma with 18F-FDG PET/CT.

BACKGROUND: The role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in the prognostication and response evaluation of primary central nervous system lymphoma (PCNSL) remains inadequately defined. METHODS: We conducted a retrospective analysis of 268 consecutive newly diagnosed patients with PCNSL between 2006 and 2020. Of these patients, 105 and 110 patients were included to evaluate the prognostic value of baseline and post-treatment 18F-FDG-PET/CT scans, respectively. Tumor uptake was considered positive when it exceeded that of the contralateral brain upon visual assessment. Quantitative analysis of baseline 18F-FDG-PET/CT included measurement of the maximal standardized uptake value (SUVmax), total metabolic tumor volume (TMTV), and total lesion glycolysis (TLG). RESULTS: The median age of the 268 patients was 62 years (range: 17-85), with 55% being male. The median progression-free survival (PFS) was 24.5 months (95% confidence interval [CI], 19.9-29.1), and the median overall survival (OS) was 34.5 months (95% CI, 22.9-46.1). The average SUVmax was 15.3 ± 5.7 and the mean TMTV and TLG were 12.6 ± 13.9 cm3 and 135.0 ± 152.7 g, respectively. Patients with a baseline TMTV ≥17.0 cm3 had significantly shorter OS (12.5 vs. 74.0 months, p=0.011). Post-treatment metabolic response by 18F-FDG-PET/CT significantly predicted PFS (median: 10.5 vs. 46.0 months, p=0.001) and OS (median: 21.0 vs. 62.0 months, p=0.002), whereas anatomic response by contrast-enhanced MRI showed no statistically significant differences in PFS (p=0.130) or OS (p=0.540). CONCLUSION: Baseline TMTV and post-treatment metabolic response, as assessed by 18F-FDG-PET/CT, are significant prognostic factors in patients with PCNSL.

Long-term outcomes of CNS WHO grade 2 oligodendroglioma in adult patients: a single-institution experience.

PURPOSE: Oligodendrogliomas (ODGs) are a subtype of diffuse lower-grade gliomas with overall survival of > 10 years. This study aims to analyze long-term outcomes and identify prognostic factors in patients with WHO grade 2 ODG. METHODS: We retrospectively reviewed 138 adult patients diagnosed with 1p/19q co-deleted ODG who underwent surgical resection or biopsy between 1994 and 2021, analyzing clinical data, treatment details, and outcomes. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier analysis. Univariate and multivariate Cox regression analyses were utilized to identify significant prognostic factors. RESULTS: In the gross total resection (GTR) group, 63 (45.7%) underwent observation and 5 (3.6%) received postoperative treatment; in the non-GTR group, 37 (26.8%) were observed and 33 (23.9%) received postoperative treatment. The median PFS and OS were 6.8 and 18.4 years, respectively. Between adjuvant treatment and observation, there was no significant difference in PFS or OS. However, GTR or STR with less than 10% residual tumor exhibited significantly better PFS and OS compared to PR or biopsy (p = 0.022 and 0.032, respectively). Multivariate analysis revealed that contrast enhancement on MRI was associated with worse PFS (HR = 2.36, p < 0.001) and OS (HR = 5.89, p = 0.001). And the presence of seizures at presentation was associated with improved OS (HR = 0.28, p = 0.006). CONCLUSION: This study underscores favorable long-term outcomes for patients with 1p/19q co-deleted ODG WHO grade 2. Our findings indicate that the EOR plays a crucial role as a significant prognostic factor in enhancing PFS and OS outcomes in WHO grade 2 ODG.

Assessment of imaging risks for recurrence after stereotactic radiosurgery for brain metastases (IRRaS-BM).

BACKGROUND: The identification of viable tumors and radiation necrosis after stereotactic radiosurgery (SRS) is crucial for patient management. Tumor habitat analysis involving the grouping of similar voxels can identify subregions that share common biology and enable the depiction of areas of tumor recurrence and treatment-induced change. This study aims to validate an imaging biomarker for tumor recurrence after SRS for brain metastasis by conducting tumor habitat analysis using multi-parametric MRI. METHODS: In this prospective study (NCT05868928), patients with brain metastases will undergo multi-parametric MRI before SRS, and then follow-up MRIs will be conducted every 3 months until 24 months after SRS. The multi-parametric MRI protocol will include T2-weighted and contrast-enhanced T1-weighted imaging, diffusion-weighted imaging, and dynamic susceptibility contrast imaging. Using k-means voxel-wise clustering, this study will define three structural MRI habitats (enhancing, solid low-enhancing, and nonviable) on T1- and T2-weighted images and three physiologic MRI habitats (hypervascular cellular, hypovascular cellular, and nonviable) on apparent diffusion coefficient maps and cerebral blood volume maps. Using RANO-BM criteria as the reference standard, via Cox proportional hazards analysis, the study will prospectively evaluate associations between parameters of the tumor habitats and the time to recurrence. The DICE similarity coefficients between the recurrence site and tumor habitats will be calculated. DISCUSSION: The tumor habitat analysis will provide an objective and reliable measure for assessing tumor recurrence from brain metastasis following SRS. By identifying subregions for local recurrence, our study could guide the next therapeutic targets for patients after SRS. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov (NCT05868928).

68Ga-DOATATOC Brain PET/CT Imaging in a case of Dural Metastasis from Synovial Sarcoma.

We present the case of a 70-year-old male patient who underwent a gallium-68 (68Ga)-DOTATOC brain positron emission tomography (PET)/computed tomography (CT) for the assessment of a tumorous lesion on the dura. The patient had previously undergone below-knee amputation due to a mass of synovial sarcoma on the left foot and completed adjuvant chemotherapy approximately 3 months ago. Subsequently, a well-demarcated papillary solid mass located on the dura was surgically excised. Pathological examination confirmed that the dural metastasis originated from synovial sarcoma and post-operative magnetic resonance imaging (MRI) revealed no residual tumor. We conducted a 68Ga-DOTATOC brain PET/CT suspecting a meningioma given the presence of a dural mass. The result showed lower uptake (maximum standardized uptake [SUVmax 4.9]) than the pituitary gland (SUVmax 9.3). Thus, we successfully conducted a differential diagnosis of metastasis from the preexisting malignancy rather than the meningioma. 68Ga-DOTATOC PET/CT is a valuable tool for the differential diagnosis of meningioma. However, metastasis should also be considered, especially in patients with a history of malignancy and lesions showing mild 68Ga-DOTATOC uptake.