Diagnostic accuracy of anti-3-[18F]-FACBC PET/MRI in gliomas.

PURPOSE: The primary aim was to evaluate whether anti-3-[18F]FACBC PET combined with conventional MRI correlated better with histomolecular diagnosis (reference standard) than MRI alone in glioma diagnostics. The ability of anti-3-[18F]FACBC to differentiate between molecular and histopathological entities in gliomas was also evaluated. METHODS: In this prospective study, patients with suspected primary or recurrent gliomas were recruited from two sites in Norway and examined with PET/MRI prior to surgery. Anti-3-[18F]FACBC uptake (TBRpeak) was compared to histomolecular features in 36 patients. PET results were then added to clinical MRI readings (performed by two neuroradiologists, blinded for histomolecular results and PET data) to assess the predicted tumor characteristics with and without PET. RESULTS: Histomolecular analyses revealed two CNS WHO grade 1, nine grade 2, eight grade 3, and 17 grade 4 gliomas. All tumors were visible on MRI FLAIR. The sensitivity of contrast-enhanced MRI and anti-3-[18F]FACBC PET was 61% (95%CI [45, 77]) and 72% (95%CI [58, 87]), respectively, in the detection of gliomas. Median TBRpeak was 7.1 (range: 1.4-19.2) for PET positive tumors. All CNS WHO grade 1 pilocytic astrocytomas/gangliogliomas, grade 3 oligodendrogliomas, and grade 4 glioblastomas/astrocytomas were PET positive, while 25% of grade 2-3 astrocytomas and 56% of grade 2-3 oligodendrogliomas were PET positive. Generally, TBRpeak increased with malignancy grade for diffuse gliomas. A significant difference in PET uptake between CNS WHO grade 2 and 4 gliomas (p < 0.001) and between grade 3 and 4 gliomas (p = 0.002) was observed. Diffuse IDH wildtype gliomas had significantly higher TBRpeak compared to IDH1/2 mutated gliomas (p < 0.001). Adding anti-3-[18F]FACBC PET to MRI improved the accuracy of predicted glioma grades, types, and IDH status, and yielded 13.9 and 16.7 percentage point improvement in the overall diagnoses for both readers, respectively. CONCLUSION: Anti-3-[18F]FACBC PET demonstrated high uptake in the majority of gliomas, especially in IDH wildtype gliomas, and improved the accuracy of preoperatively predicted glioma diagnoses. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04111588, URL: https://clinicaltrials.gov/study/NCT04111588.

Histomolecular Validation of [18F]-FACBC in Gliomas Using Image-Localized Biopsies.

BACKGROUND: Gliomas have a heterogeneous nature, and identifying the most aggressive parts of the tumor and defining tumor borders are important for histomolecular diagnosis, surgical resection, and radiation therapy planning. This study evaluated [18F]-FACBC PET for glioma tissue classification. METHODS: Pre-surgical [18F]-FACBC PET/MR images were used during surgery and image-localized biopsy sampling in patients with high- and low-grade glioma. TBR was compared to histomolecular results to determine optimal threshold values, sensitivity, specificity, and AUC values for the classification of tumor tissue. Additionally, PET volumes were determined in patients with glioblastoma based on the optimal threshold. [18F]-FACBC PET volumes and diagnostic accuracy were compared to ce-T1 MRI. In total, 48 biopsies from 17 patients were analyzed. RESULTS: [18F]-FACBC had low uptake in non-glioblastoma tumors, but overall higher sensitivity and specificity for the classification of tumor tissue (0.63 and 0.57) than ce-T1 MRI (0.24 and 0.43). Additionally, [18F]-FACBC TBR was an excellent classifier for IDH1-wildtype tumor tissue (AUC: 0.83, 95% CI: 0.71-0.96). In glioblastoma patients, PET tumor volumes were on average eight times larger than ce-T1 MRI volumes and included 87.5% of tumor-positive biopsies compared to 31.5% for ce-T1 MRI. CONCLUSION: The addition of [18F]-FACBC PET to conventional MRI could improve tumor classification and volume delineation.

The impact of resection in IDH-mutant WHO grade 2 gliomas: a retrospective population-based parallel cohort study.

OBJECTIVE: IDH-mutant diffuse low-grade gliomas (dLGGs; WHO grade 2) are often considered to have a more indolent course. In particular, in patients with 1p19q codeleted oligodendrogliomas, survival can be very long. Therefore, extended follow-up in clinical studies of IDH-mutant dLGG is needed. The authors' primary aim was to determine results after a minimum 10-year follow-up in two hospitals advocating different surgical policies. In one center early resection was favored; in the other center an early biopsy and wait-and-scan approach was the dominant management. In addition, the authors present survival and health-related quality of life (HRQOL) in stratified groups of patients with IDH-mutant astrocytoma and oligodendroglioma. METHODS: The authors conducted a retrospective, population-based, parallel cohort study with extended long-term follow-up. The inclusion criteria were histopathological diagnosis of IDH-mutant supratentorial dLGG from 1998 through 2009 in patients aged 18 years or older. Follow-up ended January 1, 2021; therefore, all patients had primary surgery more than 10 years earlier. In region A, a biopsy and wait-and-scan approach was favored, while early resections were advocated in region B. Regional referral practice ensured population-based data, since referral to respective centers was based strictly on the patient's residential address. Previous data from EQ-5D-3L, European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, and EORTC BN20 questionnaires were reanalyzed with respect to the current selection of IDH-mutant dLGG and to molecular subgroups. The prespecified primary endpoint was long-term regional comparison of overall survival. Secondarily, between-group differences in long-term HRQOL measures were explored. RESULTS: Forty-eight patients from region A and 56 patients from region B were included. Early resection was performed in 17 patients (35.4%) from region A compared with 53 patients (94.6%) from region B (p < 0.001). Characteristics at baseline were otherwise similar between cohorts. Overall survival was 7.5 years (95% CI 4.1-10.8) in region A compared with 14.6 years (95% CI 11.5-17.7) in region B (p = 0.04). When stratified according to molecular subgroups, there was only a statistically significant survival benefit in favor of early resection for patients with astrocytomas. The were no apparent differences in the different HRQOL measures between cohorts. CONCLUSIONS: In an extended follow-up of patients with IDH-mutant dLGGs, early resection was associated with a sustained and clinically relevant survival benefit. The survival benefit was not counteracted by any detectable reduction in HRQOL.

Diagnostic Value of 18 F-FACBC PET/MRI in Brain Metastases.

PURPOSE: The study aims to evaluate whether combined 18 F-FACBC PET/MRI could provide additional diagnostic information compared with MRI alone in brain metastases. PATIENTS AND METHODS: Eighteen patients with newly diagnosed or suspected recurrence of brain metastases received dynamic 18 F-FACBC PET/MRI. Lesion detection was evaluated on PET and MRI scans in 2 groups depending on prior stereotactic radiosurgery (SRS group) or not (no-SRS group). SUVs, time-activity curves, and volumetric analyses of the lesions were performed. RESULTS: In the no-SRS group, 29/29 brain lesions were defined as "MRI positive." With PET, 19/29 lesions were detected and had high tumor-to-background ratios (TBRs) (D max MR , ≥7 mm; SUV max , 1.2-8.4; TBR, 3.9-25.9), whereas 10/29 lesions were undetected (D max MR , ≤8 mm; SUV max , 0.3-1.2; TBR, 1.0-2.7). In the SRS group, 4/6 lesions were defined as "MRI positive," whereas 2/6 lesions were defined as "MRI negative" indicative of radiation necrosis. All 6 lesions were detected with PET (D max MR , ≥15 mm; SUV max , 1.4-4.2; TBR, 3.6-12.6). PET volumes correlated and were comparable in size with contrast-enhanced MRI volumes but were only partially congruent (mean DSC, 0.66). All time-activity curves had an early peak, followed by a plateau or a decreasing slope. CONCLUSIONS: 18 F-FACBC PET demonstrated uptake in brain metastases from cancer of different origins (lung, gastrointestinal tract, breast, thyroid, and malignant melanoma). However, 18 F-FACBC PET/MRI did not improve detection of brain metastases compared with MRI but might detect tumor tissue beyond contrast enhancement on MRI. 18 F-FACBC PET should be further evaluated in recurrent brain metastases.

Endoscopic third ventriculostomy for adults with hydrocephalus: creating a prognostic model for success: protocol for a retrospective multicentre study (Nordic ETV).

INTRODUCTION: Endoscopic third ventriculostomy (ETV) is becoming an increasingly widespread treatment for hydrocephalus, but research is primarily based on paediatric populations. In 2009, Kulkarni et al created the ETV Success score to predict the outcome of ETV in children. The purpose of this study is to create a prognostic model to predict the success of ETV for adult patients with hydrocephalus. The ability to predict who will benefit from an ETV will allow better primary patient selection both for ETV and shunting. This would reduce additional second procedures due to primary treatment failure. A success score specific for adults could also be used as a communication tool to provide better information and guidance to patients. METHODS AND ANALYSIS: The study will adhere to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis reporting guidelines and conducted as a retrospective chart review of all patients≥18 years of age treated with ETV at the participating centres between 1 January 2010 and 31 December 2018. Data collection is conducted locally in a standardised database. Univariate analysis will be used to identify several strong predictors to be included in a multivariate logistic regression model. The model will be validated using K-fold cross validation. Discrimination will be assessed using area under the receiver operating characteristic curve (AUROC) and calibration with calibration belt plots. ETHICS AND DISSEMINATION: The study is approved by appropriate ethics or patient safety boards in all participating countries. TRIAL REGISTRATION NUMBER: NCT04773938; Pre-results.

Variations in the management of diffuse low-grade gliomas-A Scandinavian multicenter study.

BACKGROUND: Early extensive surgery is a cornerstone in treatment of diffuse low-grade gliomas (DLGGs), and an additional survival benefit has been demonstrated from early radiochemotherapy in selected "high-risk" patients. Still, there are a number of controversies related to DLGG management. The objective of this multicenter population-based cohort study was to explore potential variations in diagnostic work-up and treatment between treating centers in 2 Scandinavian countries with similar public health care systems. METHODS: Patients screened for inclusion underwent primary surgery of a histopathologically verified diffuse WHO grade II glioma in the time period 2012 through 2017. Clinical and radiological data were collected from medical records and locally conducted research projects, whereupon differences between countries and inter-hospital variations were explored. RESULTS: A total of 642 patients were included (male:female ratio 1:4), and annual age-standardized incidence rates were 0.9 and 0.8 per 100 000 in Norway and Sweden, respectively. Considerable inter-hospital variations were observed in preoperative work-up, tumor diagnostics, surgical strategies, techniques for intraoperative guidance, as well as choice and timing of adjuvant therapy. CONCLUSIONS: Despite geographical population-based case selection, similar health care organizations, and existing guidelines, there were considerable variations in DLGG management. While some can be attributed to differences in clinical implementation of current scientific knowledge, some of the observed inter-hospital variations reflect controversies related to diagnostics and treatment. Quantification of these disparities renders possible identification of treatment patterns associated with better or worse outcomes and may thus represent a step toward more uniform evidence-based care.

Triple Use of Autologous Amnion Graft in the Treatment of Meningomyelocele and Split Cord Malformation.

This article describes the triple use of autologous amnion graft as a new procedure in the treatment of myelomeningocele and in myelomeningocele with split cord malformation. The first amnion graft was used as a physical and mechanical barrier to protect the myelomeningocele (MMC) from desiccation and mechanical stress directly after birth. A second graft was used as a dura substitute to close the cerebrospinal fluid compartment. Autologous amnion seems to be the ideal dural graft for closure of an MMC and for an MMC with split cord malformation. A tension-free and watertight closure was obtained. With the epithelium side placed to the spinal cord and due to its beneficial effect on scar formation, the risk for tethering cord syndrome is reduced when using autologous amnion as a dural graft. The regenerative properties of autologous amnion may contribute to repair neural damage. Finally, a third amnion graft was placed beneath the perforator flap used to close the skin defect to provide a watertight barrier and to stimulate flap survival.