Effects of Long-Term Temozolomide Treatment on Glioblastoma and Astrocytoma WHO Grade 4 Stem-like Cells.

Glioblastoma leads to a fatal course within two years in more than two thirds of patients. An essential cornerstone of therapy is chemotherapy with temozolomide (TMZ). The effect of TMZ is counteracted by the cellular repair enzyme O6-methylguanine-DNA methyltransferase (MGMT). The MGMT promoter methylation, the main regulator of MGMT expression, can change from primary tumor to recurrence, and TMZ may play a significant role in this process. To identify the potential mechanisms involved, three primary stem-like cell lines (one astrocytoma with the mutation of the isocitrate dehydrogenase (IDH), CNS WHO grade 4 (HGA)), and two glioblastoma (IDH-wildtype, CNS WHO grade 4) were treated with TMZ. The MGMT promoter methylation, migration, proliferation, and TMZ-response of the tumor cells were examined at different time points. The strong effects of TMZ treatment on the MGMT methylated cells were observed. Furthermore, TMZ led to a loss of the MGMT promoter hypermethylation and induced migratory rather than proliferative behavior. Cells with the unmethylated MGMT promoter showed more aggressive behavior after treatment, while HGA cells reacted heterogenously. Our study provides further evidence to consider the potential adverse effects of TMZ chemotherapy and a rationale for investigating potential relationships between TMZ treatment and change in the MGMT promoter methylation during relapse.

Implementation of European Society of Gastrointestinal Endoscopy (ESGE) recommendations for small-bowel capsule endoscopy into clinical practice: Results of an official ESGE survey.

BACKGROUND: We aimed to document international practices in small-bowel capsule endoscopy (SBCE), measuring adherence to European Society of Gastrointestinal Endoscopy (ESGE) technical and clinical recommendations. METHODS: Participants reached through the ESGE contact list completed a 52-item web-based survey. RESULTS: 217 responded from 47 countries (176 and 41, respectively, from countries with or without a national society affiliated to ESGE). Of respondents, 45 % had undergone formal SBCE training. Among SBCE procedures, 91 % were performed with an ESGE recommended indication, obscure gastrointestinal bleeding (OGIB), iron-deficiency anemia (IDA), and suspected/established Crohn's disease being the commonest and with higher rates of positive findings (49.4 %, 38.2 % and 53.5 %, respectively). A watchful waiting strategy after a negative SBCE for OGIB or IDA was preferred by 46.7 % and 70.3 %, respectively. SBCE was a second-line exam for evaluation of extent of new Crohn's disease for 62.2 % of respondents. Endoscopists adhered to varying extents to ESGE technical recommendations regarding bowel preparation ( > 60 %), use in those with pacemaker holders (62.5 %), patency capsule use (51.2 %), and use of a validated scale for bowel preparation assessment (13.3 %). Of the respondents, 67 % read and interpreted the exams themselves and 84 % classified exams findings as relevant or irrelevant. Two thirds anticipated future increase in SBCE demand. Inability to obtain tissue (78.3 %) and high cost (68.1 %) were regarded as the main limitations, and implementation of artificial intelligence as the top development priority (56.2 %). CONCLUSIONS: To some extent, endoscopists follow ESGE guidelines on using SBCE in clinical practice. However, variations in practice have been identified, whose implications require further evaluation.

Machine learning-based differentiation between multiple sclerosis and glioma WHO II°-IV° using O-(2-[18F] fluoroethyl)-L-tyrosine positron emission tomography.

INTRODUCTION: This study aimed to test the diagnostic significance of FET-PET imaging combined with machine learning for the differentiation between multiple sclerosis (MS) and glioma II°-IV°. METHODS: Our database was screened for patients in whom FET-PET imaging was performed for the diagnostic workup of newly diagnosed lesions evident on MRI and suggestive of glioma. Among those, we identified patients with histologically confirmed glioma II°-IV°, and those who later turned out to have MS. For each group, tumor-to-brain ratio (TBR) derived features of FET were determined. A support vector machine (SVM) based machine learning algorithm was constructed to enhance classification ability, and Receiver Operating Characteristic (ROC) analysis with area under the curve (AUC) metric served to ascertain model performance. RESULTS: A total of 41 patients met selection criteria, including seven patients with MS and 34 patients with glioma. TBR values were significantly higher in the glioma group (TBRmax glioma vs. MS: p = 0.002; TBRmean glioma vs. MS: p = 0.014). In a subgroup analysis, TBR values significantly differentiated between MS and glioblastoma (TBRmax glioblastoma vs. MS: p = 0.0003, TBRmean glioblastoma vs. MS: p = 0.0003) and between MS and oligodendroglioma (ODG) (TBRmax ODG vs. MS: p = 0.003; TBRmean ODG vs. MS: p = 0.01). The ability to differentiate between MS and glioma II°-IV° increased from 0.79 using standard TBR analysis to 0.94 using a SVM based machine learning algorithm. CONCLUSIONS: FET-PET imaging may help differentiate MS from glioma II°-IV° and SVM based machine learning approaches can enhance classification performance.

Dosimetric impact of the positioning variation of tumor treating field electrodes in the PriCoTTF-phase I/II trial.

PURPOSE: The aim of the present study based on the PriCoTTF-phase I/II trial is the quantification of skin-normal tissue complication probabilities of patients with newly diagnosed glioblastoma multiforme treated with Tumor Treating Field (TTField) electrodes, concurrent radiotherapy, and temozolomide. Furthermore, the skin-sparing effect by the clinically applied strategy of repetitive transducer array fixation around their center position shall be examined. MATERIAL AND METHODS: Low-dose cone-beam computed tomography (CBCT) scans of all fractions of the first seven patients of the PriCoTTF-phase I/II trial, used for image guidance, were applied for the dosimetric analysis, for precise TTField transducer array positioning and contour delineation. Within this trial, array positioning was varied from fixation-to-fixation period with a standard deviation of 1.1 cm in the direction of the largest variation of positioning and 0.7 cm in the perpendicular direction. Physical TTField electrode composition was examined and a respective Hounsfield Unit attributed to the TTField electrodes. Dose distributions in the planning CT with TTField electrodes in place, as derived from prefraction CBCTs, were calculated and accumulated with the algorithm Acuros XB. Dose-volume histograms were obtained for the first and second 2 mm scalp layer with and without migrating electrodes and compared with those with fixed electrodes in an average position. Skin toxicity was quantified according to Lyman's model. Minimum doses in hot-spots of 0.05 cm2 and 25 cm2 ( Δ D0.05cm 2 , Δ D25cm 2 ) size in the superficial skin layers were analyzed. RESULTS: Normal tissue complication probabilities (NTCPs) for skin necrosis ranged from 0.005% to 1.474% (median 0.111%) for the different patients without electrodes. NTCP logarithms were significantly dependent on patient (P < 0.0001) and scenario (P < 0.0001) as classification variables. Fixed positioning of TTField arrays increased skin-NTCP by a factor of 5.50 (95%, CI: 3.66-8.27). The variation of array positioning increased skin-NTCP by a factor of only 3.54 (95%, CI: 2.36-5.32) (P < 0.0001, comparison to irradiation without electrodes; P = 0.036, comparison to irradiation with fixed electrodes). NTCP showed a significant rank correlation with D25cm2 over all patients and scenarios (rs  = 0.76; P < 0.0001). CONCLUSION: Skin-NTCP calculation uncovers significant interpatient heterogeneity and may be used to stratify patients into high- and low-risk groups of skin toxicity. Array position variation may mitigate about one-third of the increase in surface dose and skin-NTCP by the TTField electrodes.

High-definition colonoscopy for improving adenoma detection: a systematic review and meta-analysis of randomized controlled studies.

BACKGROUND AND AIMS: Previous meta-analysis showed marginal benefit of high-definition white-light endoscopy (HD-WLE) over standard-definition colonoscopy (SDC) for adenoma detection, but with residual uncertainty due to inclusion of nonrandomized studies. We aimed to further assess the effect of HD-WLE on adenoma detection by including only randomized controlled trials (RCTs). METHODS: A literature search was performed for RCTs evaluating HD-WLE versus SDC in terms of adenoma, advanced adenoma, and serrated sessile adenoma detection rates as well as the mean number of adenomas per colonoscopy (MAC), the mean number of advanced adenomas per colonoscopy (MAAC), and the mean number of sessile serrated adenomas per colonoscopy (MSSAC). The effect size on study outcomes is presented as the risk ratio (RR; 95% confidence interval [CI]) or mean difference (MD; 95% CI). We assessed the strength of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Six RCTs involving 4594 individuals (HD-WLE, 2323; SDC, 2271) were included. Clinical indications were screening (1 study), positive result for fecal occult blood test, personal/family history of colorectal cancer (1 study), and mixed indications (4 studies). Withdrawal time was similar between the 2 arms (MD, -0.06; 95% CI, -0.25 to 0.12; P = .50). The adenoma detection rate was significantly higher in the HD-WLE arm compared with the SDC arm (40% vs 35%; RR, 1.13; 95% CI, 1.05-1.22; P = .001; I2 = 0%; GRADE, low). This effect was consistent for advanced and sessile serrated adenoma detection rates (RR, 1.33; 95% CI, 1.03-1.72; P = .03; I2 = 0%; GRADE, low; and RR, 1.55; 95% CI, 1.05-2.28; P = .03; I2 = 0%; GRADE, low, respectively). In contrast, the difference was not significant for MAC, MAAC, and MSSAC. CONCLUSIONS: Meta-analyses of RCT data support the use of HD-WLE in clinical practice, although the additional benefit is limited.

Simultaneous primary cancer occurrence of melanoma and pulmonary adenocarcinoma in leptomeningeal metastases: a case report.

BACKGROUND: Leptomeningeal metastasis (LM) is a predominantly late stage, devastating complication of a variety of malignant solid tumors. Diagnosis relies predominantly on neurological, radiographic, and cerebrospinal fluid (CSF) assessments. Recently, liquid biopsy tests derived from CSF has shown to be a feasible, noninvasive promising approach to tumor molecular profiling for proper brain cancer diagnostic treatment, thereby providing an opportunity for CSF-based personalized medicine. However, LM is typically misleadingly assumed to originate from only one primary tumor type. CASE PRESENTATION: In this case report, we provide first evidence of the co-occurrence of LM originating from more than one primary tumor types. DISCUSSION AND CONCLUSIONS: Based on this patient case profile, the co-occurrence of LM from two or more primary tumor types should be accounted for when deriving diagnostic conclusions from liquid biopsy tests.

Use of FET PET in glioblastoma patients undergoing neurooncological treatment including tumour-treating fields: initial experience.

PURPOSE: We present our first clinical experience with O-(2-18F-fluoroethyl)-L-tyrosine (FET) PET in patients with high-grade glioma treated with various neurooncological therapies including tumour-treating fields (TTFields) for the differentiation of tumour progression from treatment-related changes. METHODS: We retrospectively assessed 12 patients (mean age 51 ± 12 years, range 33-72 years) with high-grade glioma (11 glioblastomas, 1 gliosarcoma) in whom the treatment regimen included TTFields and who had undergone FET PET scans for differentiation of tumour progression from treatment-related changes. Mean and maximum tumour-to-brain ratios (TBRmean, TBRmax) were calculated. The definitive diagnosis (tumour progression or posttherapeutic changes) was confirmed either by histopathology (4 of 12 patients) or on clinical follow-up. RESULTS: In all nine patients with confirmed tumour progression, the corresponding FET PET showed increased uptake (TBRmax 3.5 ± 0.6, TBRmean 2.7 ± 0.7). In one of these nine patients, FET PET was consistent with treatment-related changes, whereas standard MRI showed a newly diagnosed contrast-enhancing lesion. In two patients treated solely with TTFields without any other concurrent neurooncological therapy, serial FET PET revealed a decrease in metabolic activity over a follow-up of 6 months or no FET uptake without any signs of tumour progression or residual tumour on conventional MRI. CONCLUSION: FET PET may add valuable information in monitoring therapy in individual patients with high-grade glioma undergoing neurooncological treatment including TTFields.

The role of surgical treatment in isolated organ recurrence of esophageal cancer-a systematic review of the literature.

BACKGROUND: Despite the improvements in the early detection and treatment of non-metastatic esophageal cancer, more than half of patients undergoing a curative treatment for esophageal cancer will develop recurrence within three years. The prognosis of these patients is poor. However, a wide range in overall survival has been reported, depending on the pattern of recurrence, and no optimal treatment strategy following recurrence has yet been uniformly accepted. AIM: In this article, we aimed to systematically review the literature for the role of surgical resection of metachronous distant metastasis following primary treatment of esophageal cancer. Furthermore, we discuss possible factors that could possibly predict which patients may benefit from a surgical approach. A comprehensive literature search was conducted in PubMed using combinations of keywords. RESULTS: Patients with recurrence may benefit of a multimodality treatment. Regarding the isolated recurrence of esophageal cancer in solid visceral organs, operative intervention has been proposed as a treatment that may offer a survival benefit in an individual basis. No definitive conclusions regarding the potential survival advantage offered by the surgical treatment of solitary recurrent lesions can be drawn. However, recent improvements in surgical treatment and optimization of perioperative management guarantee an acceptable operative risk, making surgical resection of solitary recurrence lesions a considerable therapeutic option. CONCLUSIONS: It can be conferred from the available studies that the surgical treatment of isolated recurrence from esophageal cancer may offer a survival benefit for properly selected patients. Prospective, multicenter studies might be useful to gain a better insight into those factors that affect selection of patients to take benefit from an operative intervention.

Gastric carcinosarcoma: a rare clinical entity looking for an identity.

Carcinosarcoma of the stomach represents a rare variant of gastric malignancies. It is composed of intimately mixed epithelial and mesenchymal elements. Only few cases of gastric carcinosarcoma have been reported in the literature. Surgical treatment is the only curative modality, but the disease progress is usually aggressive and its prognosis remains poor even afer curative treatment. The defnitive diagnosis is usually made by histopathological and immunohistochemical analysis of the resected tumor. This review summarizes the available data concerning epidemiology, pathogenesis, clinical characteristics, diagnosis, histopathology, treatment and prognosis of gastric carcinosarcoma.

Activation of NLRP3 Inflammasome in Inflammatory Bowel Disease: Differences Between Crohn's Disease and Ulcerative Colitis.

BACKGROUND: NLRP3 inflammasome is a multimolecular cytosol complex that, when activated, contributes to the cleavage of pro-interleukin (IL)-1ß to IL-1ß. AIMS: To investigate NLRP3 inflammasome activation in inflammatory bowel disease. METHODS: Peripheral blood mononuclear cells from Crohn's disease (CD), ulcerative colitis (UC) patients and controls were stimulated with LPS in the absence or presence of MSU. After incubation, concentrations of IL-1ß, IL-6, and TNFα were measured in cell supernatants and concentration of pro-IL-1ß was measured in cell lysates. NLRP3 activation was defined as more than 30% increase in IL-1ß production after MSU addition. In separate experiments, PBMCs were lysed for RNA isolation transcripts of IL-1ß, TNFα, NLRP3, and CASP1 were measured by RT-PCR. DNA was isolated from CD patients for ATG16L1 gene genotyping. RESULTS: NLRP3 inflammasome was activated in 60% of CD patients compared to 28.6% of controls (p = 0.042); no significant difference was detected between UC and controls. Among UC patients, NLRP3 activation was associated (p = 0.008) with long-standing disease (>1.5 years). IL-1ß levels were significantly higher in CD patents in comparison with controls (p = 0.032). No difference was detected in the levels of IL-6, TNFα, pro-IL-1ß and in the numbers IL-1ß, TNFα, NLRP3, and CASP1 transcripts among groups. IL-1ß production was similar between carriers of wild-type and of SNP alleles of the rs2241880. CONCLUSIONS: NLRP3 inflammasome is activated in CD patients and in UC patients with long-standing disease.

[Headache News]. / Neues bei Kopfschmerzen.

A review of the latest and most relevant information on different disorders of head and facial pain is presented. News from epidemiologic studies regarding the relationship between migraine and patent foramen ovale, the cardiovascular risk in migraine, and migraine behavior during menopause, and the development of white matter lesions or migraine genetics are presented. Regarding pathophysiology there are very recent insights regarding the role of the hypothalamus during prodromal phase and the interplay of brain-stem and hypothalamus during the attack. In the last year studies and metaanalysis generated new knowledge for the use of triptans in general as in menstrual related migraine and hemiplegic variants. Furthermore, new hope rises for the CGRP (calcitonin-gene related peptide)-antagonists, as the data for ubrogepant do not suggest hepatotoxicity but efficacy. In prophylactic migraine treatment the news are manly on how the new therapeutic approach with monoclonal antibodies against CGRP or its receptor is moving on. Additional newly generated data for already known prophylactic agents as for new approaches are compactly discussed. Although main developments in headache focus on migraine new data on trigemino-autonomic headache trigeminal neuralgia and new daily persistant headache became available.

The Role of Fibroblast Activation Protein in Glioblastoma and Gliosarcoma: A Comparison of Tissue, 68Ga-FAPI-46 PET Data, and Survival Data.

Despite their unique histologic features, gliosarcomas belong to the group of glioblastomas and are treated according to the same standards. Fibroblast activation protein (FAP) is a component of a tumor-specific subpopulation of fibroblasts that plays a critical role in tumor growth and invasion. Some case studies suggest an elevated expression of FAP in glioblastoma and a particularly strong expression in gliosarcoma attributed to traits of predominant mesenchymal differentiation. However, the prognostic impact of FAP and its diagnostic and therapeutic potential remain unclear. Here, we investigate the clinical relevance of FAP expression in gliosarcoma and glioblastoma and how it correlates with 68Ga-FAP inhibitor (FAPI)-46 PET uptake. Methods: Patients diagnosed with gliosarcoma or glioblastoma without sarcomatous differentiation with an overall survival of less than 2.5 y were enrolled. Histologic examination included immunohistochemistry and semiquantitative scoring of FAP (0-3, with higher values indicating stronger expression). Additionally, 68Ga-FAPI-46 PET scans were performed in a subset of glioblastomas without sarcomatous differentiation patients. The clinical SUVs were correlated with FAP expression levels in surgically derived tumor tissue and relevant prognostic factors. Results: Of the 61 patients who were enrolled, 13 of them had gliosarcoma. Immunohistochemistry revealed significantly more FAP in gliosarcomas than in glioblastomas without sarcomatous differentiation of tumor tissue (P < 0.0001). In the latter, FAP expression was confined to the perivascular space, whereas neoplastic cells additionally expressed FAP in gliosarcoma. A significant correlation of immunohistochemical FAP with SUVmean and SUVpeak of 68Ga-FAPI-46 PET indicates that clinical tracer uptake represents FAP expression of the tumor. Although gliosarcomas express higher levels of FAP than do glioblastomas without sarcomatous differentiation, overall survival does not significantly differ between the groups. Conclusion: The analysis reveals a significant correlation between SUVmean and SUVpeak in 68Ga-FAPI-46 PET and immunohistochemical FAP expression. This study indicates that FAP expression is much more abundant in the gliosarcoma subgroup of glioblastomas. This could open not only a diagnostic but also a therapeutic gap, since FAP could be explored as a theranostic target to enhance survival in a distinct subgroup of high-risk brain tumor patients with poor survival prognosis.

Are we providing best-available care to newly diagnosed glioblastoma patients? Systematic review of phase III trials in newly diagnosed glioblastoma 2005-2022.

Background: Glioblastoma is the most aggressive primary brain cancer with a poor prognosis. Despite numerous studies in the past 17 years, effective treatment options for glioblastoma remain limited. In this study, we aimed to identify and compare phase III clinical trials for glioblastoma in terms of efficacy and baseline characteristics. Methods: A systematic literature search was conducted using PubMed and ClinicalTrials.gov to identify phase III clinical trials for glioblastoma in adult patients. The target population included adult patients aged 18 years and above (younger cohort) and patients ≥60 years of age (elderly cohort). The search results were screened based on predefined inclusion criteria, and the included trials were analyzed for their study design, baseline characteristics, and survival results. Results: Eleven trials met the inclusion criteria in the younger cohort. Of these, three reported a statistically significant improvement in overall survival (OS), including the EORTC/NCIC study (NCT00006353), EF-14 (NCT00916409), and CeTeG (NCT01149109). Of the 11 trials, eight were open-label randomized trials, including all of the positive ones, while three negative trials employed treatment blinding and a placebo control. The baseline characteristics of the trials [such as extent of resection, age, gender, and O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status] did not significantly differ between positive and negative trials. Isocitrate dehydrogenase (IDH) mutation status was analyzed in only two trials, with a small percentage of IDH-mutated tumors in each. Additionally, three more trials in the elderly cohort showed a statistically significant improvement of OS, the NOA-08 trial, the ISRCTN81470623-trial by Malmström et al. and NCT00482677-trial by Perry et al. Their baseline characteristics and implications are also analyzed. Conclusion: This analysis of phase III clinical trials for glioblastoma conducted since 2005 showed that the majority of trials did not result in a significant improvement in OS. Among the trials included in this analysis, only the EORTC/NCIC, EF-14, and CeTeG studies demonstrated a positive OS outcome in the younger cohort.

Precision neuro-oncology: a pilot analysis of personalized treatment in recurrent glioma.

PURPOSE: When brain cancer relapses, treatment options are scarce. The use of molecularly matched targeted therapies may provide a feasible and efficacious way to treat individual patients based on the molecular tumor profile. Since little information is available on this strategy in neuro-oncology, we retrospectively analyzed the clinical course of 41 patients who underwent advanced molecular testing at disease relapse. METHODS: We performed Sanger sequencing, targeted next generation sequencing, and immunohistochemistry for analysis of potential targets, including programmed death ligand 1, cyclin D1, phosphorylated mechanistic target of rapamycin, telomerase reverse transcriptase promoter mutation, cyclin-dependent kinase inhibitor 2A/B deletion, or BRAF-V600E mutation. In selected patients, whole exome sequencing was conducted. RESULTS: The investigation included 41 patients, of whom 32 had isocitrate dehydrogenase (IDH) wildtype glioblastoma. Molecular analysis revealed actionable targets in 31 of 41 tested patients and 18 patients were treated accordingly (matched therapy group). Twenty-three patients received molecularly unmatched empiric treatment (unmatched therapy group). In both groups, 16 patients were diagnosed with recurrent IDH wildtype glioblastoma. The number of severe adverse events was comparable between the therapy groups. Regarding the IDH wildtype glioblastoma patients, median progression-free survival (mPFS) and median overall survival (mOS) were longer in the matched therapy group (mPFS: 3.8 versus 2.0 months, p = 0.0057; mOS: 13.0 versus 4.3 months, p = 0.0357). CONCLUSION: These encouraging data provide a rationale for molecularly matched targeted therapy in glioma patients. For further validation, future study designs need to additionally consider the prevalence and persistence of actionable molecular alterations in patient tissue.

Feasibility and tolerability of trofosfamide and etoposide in progressive glioblastoma.

Background: Standard of care treatment options at glioblastoma relapse are still not well defined. Few studies indicate that the combination of trofosfamide plus etoposide may be feasible in pediatric glioblastoma patients. In this retrospective analysis, we determined tolerability and feasibility of combined trofosfamide plus etoposide treatment at disease recurrence of adult glioblastoma patients. Methods: We collected clinicopathological data from adult progressive glioblastoma patients treated with the combination of trofosfamide and etoposide for more than four weeks (one course). A cohort of patients receiving empiric treatment at the investigators' discretion balanced for tumor entity and canonical prognostic factors served as control. Results: A total of n = 22 progressive glioblastoma patients were eligible for this analysis. Median progression-free survival (3.1 vs 2.3 months, HR: 1.961, 95% CI: 0.9724-3.9560, P = .0274) and median overall survival (9.0 vs 5.7 months, HR: 4.687, 95% CI: 2.034-10.800, P = .0003) were significantly prolonged compared to the control cohort (n = 17). In a multivariable Cox regression analysis, treatment with trofosfamide plus etoposide emerged as a significant prognostic marker regarding progression-free and overall survival. We observed high-grade adverse events in n = 16/22 (73%) patients with hematotoxicity comprising the majority of adverse events (n = 15/16, 94%). Lymphopenia was by far the most commonly observed hematotoxic adverse event (n = 11/15, 73%). Conclusions: This study provides first indication that the combination of trofosfamide plus etoposide is safe in adult glioblastoma patients. The observed survival outcomes might suggest potential beneficial effects. Our data provide a reasonable rationale for follow-up of a larger cohort in a prospective trial.

Telemedicine in Neuro-Oncology-An Evaluation of Remote Consultations during the COVID-19 Pandemic.

In order to minimize the risk of infections during the COVID-19 pandemic, remote video consultations (VC) experienced an upswing in most medical fields. However, telemedicine in neuro-oncology comprises unique challenges and opportunities. So far, evidence-based insights to evaluate and potentially customize current concepts are scarce. To fill this gap, we analyzed >3700 neuro-oncological consultations, of which >300 were conducted as VC per patients' preference, in order to detect how both patient collectives distinguished from one another. Additionally, we examined patients' reasons, suitable/less suitable encounters, VC's benefits and disadvantages and future opportunities with an anonymized survey. Patients that participated in VC had a worse clinical condition, higher grade of malignancy, were more often diagnosed with glioblastoma and had a longer travel distance (all p < 0.01). VC were considered a fully adequate alternative to face-to-face consultations for almost all encounters that patients chose to participate in (>70%) except initial consultations. Most participants preferred to alternate between both modalities rather than participate in one alone but preferred VC over telephone consultation. VC made patients feel safer, and participants expressed interest in implementing other telemedicine modalities (e.g., apps) into neuro-oncology. VC are a promising addition to patient care in neuro-oncology. However, patients and encounters should be selected individually.

BRMS1 in Gliomas-An Expression Analysis.

The metastatic suppressor BRMS1 interacts with critical steps of the metastatic cascade in many cancer entities. As gliomas rarely metastasize, BRMS1 has mainly been neglected in glioma research. However, its interaction partners, such as NFκB, VEGF, or MMPs, are old acquaintances in neurooncology. The steps regulated by BRMS1, such as invasion, migration, and apoptosis, are commonly dysregulated in gliomas. Therefore, BRMS1 shows potential as a regulator of glioma behavior. By bioinformatic analysis, in addition to our cohort of 118 specimens, we determined BRMS1 mRNA and protein expression as well as its correlation with the clinical course in astrocytomas IDH mutant, CNS WHO grade 2/3, and glioblastoma IDH wild-type, CNS WHO grade 4. Interestingly, we found BRMS1 protein expression to be significantly decreased in the aforementioned gliomas, while BRMS1 mRNA appeared to be overexpressed throughout. This dysregulation was independent of patients' characteristics or survival. The protein and mRNA expression differences cannot be finally explained at this stage. However, they suggest a post-transcriptional dysregulation that has been previously described in other cancer entities. Our analyses present the first data on BRMS1 expression in gliomas that can provide a starting point for further investigations.

Location of Recurrences after Trimodality Treatment for Glioblastoma with Respect to the Delivered Radiation Dose Distribution and Its Influence on Prognosis.

BACKGROUND: While prognosis of glioblastoma after trimodality treatment is well examined, recurrence pattern with respect to the delivered dose distribution is less well described. Therefore, here we examine the gain of additional margins around the resection cavity and gross-residual-tumor. METHODS: All recurrent glioblastomas initially treated with radiochemotherapy after neurosurgery were included. The percentage overlap of the recurrence with the gross tumor volume (GTV) expanded by varying margins (10 mm to 20 mm) and with the 95% and 90% isodose was measured. Competing-risks analysis was performed in dependence on recurrence pattern. RESULTS: Expanding the margins from 10 mm to 15 mm, to 20 mm, to the 95%- and 90% isodose of the delivered dose distribution with a median margin of 27 mm did moderately increase the proportion of relative in-field recurrence volume from 64% to 68%, 70%, 88% and 88% (p < 0.0001). Overall survival of patients with in-and out-field recurrence was similar (p = 0.7053). The only prognostic factor significantly associated with out-field recurrence was multifocality of recurrence (p = 0.0037). Cumulative incidences of in-field recurrences at 24 months were 60%, 22% and 11% for recurrences located within a 10 mm margin, outside a 10 mm margin but within the 95% isodose, or outside the 95% isodose (p < 0.0001). Survival from recurrence was improved after complete resection (p = 0.0069). Integrating these data into a concurrent-risk model shows that extending margins beyond 10 mm has only small effects on survival hardly detectable by clinical trials. CONCLUSIONS: Two-thirds of recurrences were observed within a 10 mm margin around the GTV. Smaller margins reduce normal brain radiation exposure allowing for more extensive salvage radiation therapy options in case of recurrence. Prospective trials using margins smaller than 20 mm around the GTV are warranted.

Evaluation of [68Ga]-DOTATOC PET/MRI in Patients with Meningioma of the Subcranial and Intraorbital Space.

Meningiomas are known to express somatostatin receptor (SSTR) type 2 to a high degree. Therefore, radiolabeled somatostatin analogs, such as DOTATOC, have been introduced for PET imaging of meningiomas. However, the benefit of hybrid SSTR PET/MRI is still debated. Here, we report our experience with [68Ga]-DOTATOC PET/MRI. Methods: PET/MRI was performed in 60 patients with suspected or diagnosed meningiomas of the skull plane and eye socket. Acquired datasets were reported by 2 independent readers regarding local tumor extent and signal characteristics. Histopathologic results and follow-up imaging served as the reference standard. SUVs of target lesions were analyzed according to the corresponding maximal tracer uptake. The diagnostic accuracy of PET/MRI and conventional MRI was determined independently and compared with the reference standard. Results: In total, 60 target lesions were identified, with 54 considered to be meningiomas according to the reference standard. Sensitivity and specificity of PET/MRI versus MRI alone were 95% versus 96% and 75% versus 66%, respectively. The McNemar test was not able to distinguish any differences between PET/MRI and the reference standard or MRI and the reference standard. No differences were found between the 2 modalities with respect to local infiltration. Conclusion: SSTR PET/MRI and MRI yielded similar accuracy for the detection of meningiomas of the skull base and intraorbital space. Here, sequential low-dose SSTR PET/CT might be helpful for the planning of radioligand therapy or radiotherapy.