KS04.6.A Epidemiology of adult meningioma in the Netherlands: a population-based study

alexandrossfakianakis shared this article with you from Inoreader KS04.6.A Epidemiology of adult meningioma in the Netherlands: a population-based study via # Neuro-Oncology Current Issue Abstract Background Meningiomas are the most common primary tumours of the central nervous system. As the majority of meningiomas are benign, initial management often consists of observation only. Consequently, estimates on meningioma incidence are generally considered too low, with many registries mainly depending on pathology notifications. With additional notification sources, this study provides more complete population-based estimates on the incidence, prevalence, and prognostic impact of meningioma diagnosis in the Netherlands. Material and Methods Data on patients diagnosed with meningioma during 2000-2019 were obtained from the Netherlands Cancer Registry (NCR), which was expanded to the Dutch Brain Tumour Registry (DBTR) for meningiomas as of 2016. In addition to histological confirmations, the NCR/DBTR receives case notifications from hospital administrative registrations on cost reimbursement and outpatient care. In addition, a data linkage was performed with a clinical database maintained by one of the Dutch neuro-oncology centres to evaluate local completeness of the NCR/DBTR. Time trends of the age-adjusted incidence rates were evaluated by calculating the estimated annual percentage change (EAPC). Relative survival rates were calculated using the Pohar-Perme estimator. Results From 2000 to 2019, a total of 22,605 cases of meningioma were registered; 11,423 (50.5%) were histologically confirmed, while 11,182 (49.5%) had a radiological diagnosis. Over time, incidence increased from 4.7 per 100,000 inhabitants (European Standardized Rate, ESR) to 10.7 (EAPC 4.6%, p<0.01); the incidence of radiological diagnosis increased from 1.2 to 6.9 per 100,000 ESR (EAPC 9.6%, p<0.01). Local data completeness was estimated at 98% for histologically confirmed meningiomas and 87% for radiological diagnoses. On the basis of these incidence estimates, the prevalence of meningioma is estimated at 105/100, 000 on January 1st of 2020, with over 17,500 individuals having had a diagnosis of meningioma at that moment. Relative survival rate at 5 years for grade I meningiomas was 94.8% (95%-confidence interval: 94.0%-95.4%), 84.0% (95%CI: 81.0%-86.5%) for grade II meningiomas, and 47.3% (95%CI: 38.2%-55.8%) for grade III meningiomas. Conclusion As the incidence estimates in this study may be considered most complete, the results obtained should approximate the true incidence, prevalence, and prognostic impact of meningioma diagnosis in the Netherlands. View on Web

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P12.10.A Supratentorial glioblastoma with spinal metastasis: a case report with molecular profiling

alexandrossfakianakis shared this article with you from Inoreader P12.10.A Supratentorial glioblastoma with spinal metastasis: a case report with molecular profiling via # Neuro-Oncology Current Issue Abstract Background Glioblastoma (GBM) is regarded as an aggressive brain tumor that rarely develops extracranial metastases. Despite well-investigated molecular alterations in GBM, there is a limited understanding of these associated with the metastatic potential of GBM. Material and Methods We present a case report of a 43-year-old woman with frontal GBM IDH-wildtype, who underwent gross-total resection followed by chemoradiation. Five months after surgery, the patient was diagnosed with an intraspinal GBM metastasis. Next-generation sequencing analysis of both primary and metastatic GBM tissues was performed using the Illumina TruSight Tumor 170 assay. Results The number of single nucleotide variants observed in the metastatic sample was more than 2-times higher. Mutations in TP53, PTEN, and RB1 found in the primary and metastatic tissue samples are indicative of the mesenchymal GBM subtype. Among others, in the metastatic s ample, there were detected two inactivating mutations (Arg1026Ile, Trp1831Ter) in the NF1 gene, two novel NOTCH3 variants of unknown significance predicted to be damaging (Pro1505Thr, Cys1099Tyr), one novel ARID1A variant of unknown significance (Arg1046Ser), and one gene fusion of unknown significance EIF2B5-KIF5B. Conclusion Based on the literature evidence, the inactivation of NF1, NOTCH3, and ARID1A could explain, at least in part, the acquired invasiveness and metastatic potential in this particular GBM case.This work was supported by the grant MUNI/A/1408/2021 of the Masaryk University, Brno, Czech Republic, and INTER-EXCELLENCE Programme / INTER-COST project no. LTC20027 of the Ministry of Health, Czech Republic. View on Web

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P11.75.B Survival benefit of radiotherapy and surgery in patients with lung cancer brain metastases with poor prognosis factors

alexandrossfakianakis shared this article with you from Inoreader P11.75.B Survival benefit of radiotherapy and surgery in patients with lung cancer brain metastases with poor prognosis factors via # Neuro-Oncology Current Issue Abstract Background Radiotherapy and surgery are the standard treatments for lung cancer brain metastases (BMs). However, limitted studies focused on the treatments for patients with lung cancer BMs with poor prognosis factors. The purpose of this study was to investigate the effects of radiotherapy and surgery in patients with lung cancer BMs with poor prognosis factors, providing reference for clinical strategies. Material and Methods We analyzed retrospectively 714 patients with lung cancer BMs. A 1:1 propensity score matching (PSM) was performed to balance potential confounders. Analyses of overall survival (OS) and risk factors for OS were assessed by log-rank test and Cox proportional hazard model. Results Age ≥65 years, Karnofsky Performance Scale (KPS) score ≤70, anaplastic large-cell lymphoma kinase (ALK)/epidermal growth factor receptor (EGFR) wild type, extracranial metastases, non-surgery and non-radiotherapy le d to poor prognosis. Patients were stratified according to these factors. Radiotherapy and surgery showed no survival benefit in patients with aged ≥65 years or pretreatment KPS score ≤70 before and after PSM. Before PSM, whole brain radiotherapy (WBRT) improved the OS and predicted good prognosis in patients with ALK/EGFR wild type or extracranial metastases. WBRT also predicted good prognosis in patients with non-surgery. Stereotactic radiosurgery (SRS) improved the OS and predicted good prognosis in patients with ALK/EGFR wild type or non-surgery. WBRT plus SRS improved the OS and predicted good prognosis in patients with extracranial metastases or non-surgery. WBRT plus SRS also predicted good prognosis in patients with ALK/EGFR wild type. Surgery improved the OS and predicted good prognosis in patients with non-radiotherapy. After PSM, SRS improved the OS and predicted good prognosis in patients with non-surgery. WBRT plus SRS improved the OS and predicted good prognosis in patients with non-surgery or extracranial metastases. WBRT plus SRS also predicted good prognosis in patients with ALK/EGFR wild type. Surgery improved the OS of patients with non-radiotherapy. We defined that the treatment would provide significant survival benefit if it both prolonged the OS and predicted good prognosis. Meanwhile, the results after PSM were more convincing than the results before PSM. Conclusion Radiotherapy has significant survival benefit in patients with lung cancer BMs with poor prognosis factors, including patients with ALK/EGFR wild type or extracranial metastases or non-surgery. Surgery only has significant survival benefit in patients with non-radiotherapy. View on Web

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P11.74.A Plexiform Neurofibromas prevalence and treatment modalities in a referral comprehensive cancer center

alexandrossfakianakis shared this article with you from Inoreader P11.74.A Plexiform Neurofibromas prevalence and treatment modalities in a referral comprehensive cancer center via # Neuro-Oncology Current Issue Abstract Background Neurofibromatosis type 1 (NF1) is the most common tumor predisposition syndrome, with an incidence of 1/3500. Plexiform neurofibromas (PN) are benign tumors that can occur along the nerve sheath throughout the body, with unpredictable growth and with risk of malignant transformation. Symptoms will depend on their size and location, and include pain, deformity and functional impairment. There is a great variability in the PN severity and impact on quality-of-life (QOL). An unknown percentage of NF1 patients may need treatment, either medical and/or surgical. Objectives To assess the frequency of PN in a NF1 population followed in a comprehensive cancer center. Material and Methods Retrospective study. All patients with NF1 and PN followed in our center, between 31/12/2000 and 31/12/2021. Results Of 438 NF1 patients, 185 had PN (42%). 52 NF1 patients with PN were children (≤ 18). The most common sym ptoms were pain in 71 people (38,4%), deformity in 70 (37,8%) and functional impairment in 69 (37,3%). Several patients had a combination of these symptoms. Different treatment modalities were used for PN: medical, surgical or both. In this study, 54 patients (29,1%) were treated with MEK inhibitors (selumetinib), 74 patients (40%) were treated surgically and 12,4% (23) needed a combined approach (medical and surgical treatment). Conclusion PN are frequent in NF1 patients. A significant percentage is symptomatic and will require treatment, surgical, medical or both. There is no standard of care for PN NF1. The timing and sequence of medical and surgical treatment is yet to be defined. View on Web

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P11.73.B The diagnostic value of frame-based stereotactic biopsies in the age of precision oncology: A cross-sectional study

alexandrossfakianakis shared this article with you from Inoreader P11.73.B The diagnostic value of frame-based stereotactic biopsies in the age of precision oncology: A cross-sectional study via # Neuro-Oncology Current Issue Abstract Background For non-resectable, eloquent, multifocal and deep-seated intracranial lesions, stereotactic frame-based biopsies can deliver a finite amount of tissue for neuropathology studies. With the increasing role of molecular genetics in the diagnostics of intracranial tumors, sufficient tissue for sequencing studies is of paramount importance. This study explored the rate of successful diagnosis after stereotactic frame-based biopsies of intracranial lesions in a high-throughput neurooncology center Material and Methods 145 consecutive patients undergoing frame-based stereotactic biopsies in 2020 and 2021 at our neurosurgical department were included in this retrospective analysis. Aspects of histological and molecular (methylomics, panel-sequencing) neuropathology analysis in addition to clinical and radiological variables were analyzed. Cases were classified as conclusive, likely-conclusive (sufficient diagnosis with non-s atisfying sequencing information), and inconclusive neuropathological diagnosis. Results Of 145 cases analyzed, astrocytic tumors were suspected in n= 94 (67%) of patients. In n= 122 cases (84%), a conclusive diagnosis was possible. For 14 (11%) cases, a likely-conclusive diagnosis was established Diagnoses comprised mainly WHO 4 glioblastomas (56%), WHO 3 gliomas (2%) in addition to WHO 1 and 2 gliomas (n=7, 5%), CNS lymphomas (n=23, 16%), inflammatory diseases (n=10, 7%) and normal or reactive tissue (n=4, 3%). Methylomics were pivotal in providing an integrated diagnosis in 30% of the cases (panel sequencing in 14%). In n= 12 (8%) of the cases further testing was hindered by insufficient tissue sample DNA. Only in 3 out of 12 cases this resulted in a final inconclusive diagnosis. Conclusion Although stereotactic frame-based biopsies deliver a limited amount of tissue, they bear an excellent histopathological and molecular genetic diagnostic yield, with rare case s of missing molecular data or rarely insufficient diagnosis. Optimizing the number and representativeness of cell and DNA-rich stereotactic biopsy specimen might enhance the diagnostic and therapeutic potential of precision oncology even further. View on Web

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P11.71.B Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) in a patient with blastic plasmacytoid dendritic cell neoplasm: a rare neurologic manifestation in a rare disease

alexandrossfakianakis shared this article with you from Inoreader P11.71.B Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) in a patient with blastic plasmacytoid dendritic cell neoplasm: a rare neurologic manifestation in a rare disease via # Neuro-Oncology Current Issue Abstract Background Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare aggressive myeloid hematological malignancy. Skin lesions, bone marrow, lymph nodes or visceral organs can be involved. 30% of patients will have infiltration to the nervous system,occult asymptomatic infiltration is frequent. Immunophenotype express CD4, CD56, and CD123, and flow cytometry is essential. Material and Methods 70-yo Hispanic male with a 1-month history of multiple violaceous cutaneous nodules and adenopathies.Neurological complaints included diplopia, hypoesthesia in the left face, dysphagia, gait difficulties, and generalized weakness with distal hypoesthesia. Examination revealed multiple cranial neuropathy (bilateral VI and VII nerve palsies, left V3 and VIII palsies and IX, X involvement), global areflexia, length-dependent weakness, ataxic gait and cerebellar syndrome. An inguinal ganglionar biopsy retrieved cells positive for CD4, TCL 1, CD68 and CD123, whereas CD3, CD20, CD7, CD8, CD30 and myeloperoxidase were negative. PET/CT showed multiple supra and infradiaphragmatic adenopathies, bilateral pleural, pericardial and abdominal implants. Bone marrow biopsy was negative. Brain MRI showed contrast enhancement in the cerebellar folia and in the roots of the cranial nerves clinically involved. Multiple CSFs demonstrated high protein count (281- 310mg/dl), normal glucose and cell count; CSF flow cytometry and cytology reported no blastic infiltration (negative CD4, CD56 and CD123), CSF onconeuronal antibodies were negative. Nerve conduction studies fulfilled definite electrodiagnostic EFNS criteria for CIDP. Sural nerve biopsy reported inflammatory demyelination without infiltration. Systemic chemotherapy (Cyclophosphamide/Vincristine) with intrathecal cytarbine/methotrexate was administered. Results Favorable initial, but brief response was noticed for the cranial nerves and gait. He had neurological relap se with gait impossibility. Neuraxis MRI showed no contrast enhancement in the brain but new contrast enhancement of lumbosacral roots. Nerve conduction studies reported severe worsening criteria of CIDP. The PET/CT demonstrated complete response. Five days of methylprednisolone (1gr IV) followed by oral prednisone were prescribed (50 mg qd). However, two weeks later he suffered clinical neurological worsening with respiratory failure. IVIg was started (.4g/kg/day for 5 days) with no improvement; palliative care decision was consented. Conclusion We report the case of an adult male with multiple cranial nerve palsy, cerebellar syndrome and refractory rapidly progressive asymmetric polyneuropathy with BPDCN. CIDP in the absence of multiple attempts to demonstrate nervous system infiltration led us to consider this as a paraneoplastic phenomenon refractory to treatment. To our knowledge no CIDP has been reported in this rare disease View on Web

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P17.11.A Experience of ketogenic diet with support of liquid formula 3:1 and high-grade gliomas: Case series

alexandrossfakianakis shared this article with you from Inoreader P17.11.A Experience of ketogenic diet with support of liquid formula 3:1 and high-grade gliomas: Case series via # Neuro-Oncology Current Issue Abstract Background High-grade gliomas, including glioblastoma, are the most common primary malignant brain tumors in adults. Despite the efforts to develop new therapies, treatment options remain limited and the prognosis is poor. Ketogenic diet, is an emerging complementary therapy for high-grade gliomas. It is hypothesized that through the change of the energy source from glucose to ketones and the inability of glioma cells to metabolize ketone bodies with the same ease due to inefficient oxidative phosphorylation, tumor growth is slowed. The feasibility of a ketogenic diet is a matter of concern. Its influence on the quality of life of patients with advanced cancers showing that even though it may cause constipation and reflux, quality of life is generally not affected Material and Methods We reported a case series of patients with high-grade gliomas using ketogenic diet with liquid formula 3:1 ratio (KDS) as a complementary treatme nt. We describe baseline characteristics, and EORTC-QLQ30 score and symptom evaluation Results We describe the case of 3 patients (2 women and 1 man) with diagnoses of grade 4 glioblastoma (2) and grade 3 oligodendroglioma (1), mean age 46.7 years (38- 56 years), ECOG 1 (2) and ECOG2 (1), gross tumor resection (1 glioblastoma patient), subtotal resection (1 glioblastoma patient), and biopsy (1 oligodendroglioma patient). All patients received radiotherapy, 66.7% (n=2) stupp protocol, and 33.3% (n=1) received hypofractionated therapy and adjuvant treatment with temozolomide. All patients received first line with temozolomide, and 33.3% received a total of four lines of chemotherapy. All the patients were fed orally and managed with KDS at the last progression. Median follow up time was 4 months. KDS didn't impact corporal weight and a positive impact was noted in seizure episodes (> 3 per day before vs < 3 per day after DKS) and quality of life (EORTC-QLQ30 61,3 [60 - 66,8] at the begining vs 70,9 [69,8 - 71,2] at the last visit). Regarding tolerance, one patient presented diarrhea and/or constipation grade 1 the first 5 days of treatment. Compliance was measured by days with a median adherence of 90%. Current disease status is stable disease (RANO criteria) in the three patients. Conclusion KDS could be an interesting therapy complementary to standard treatment in patients with high grade gliomas, especially in those patients who debut with seizures, improving quality of life and number of convulsive crises. More studies in adult patients are required to confirm this hypothesis View on Web

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P17.09.A Regorafenib and Re-irradiation: analysis of clinical outcomes and toxicities in patients with recurrent glioblastomas

alexandrossfakianakis shared this article with you from Inoreader P17.09.A Regorafenib and Re-irradiation: analysis of clinical outcomes and toxicities in patients with recurrent glioblastomas via # Neuro-Oncology Current Issue Abstract Background Glioblastoma is the most common and aggressive primary brain tumor in adults.The aggressiveness and poor prognosis related to this disease join to the limited available treatment options. The current standard of care involves surgical resection followed by concomitant radiotherapy and chemotherapy. At recurrence, no standard treatment exists and there are no guidelines to facilitate decisions in the recurrent setting. Available options include re-operation, re-irradiation, systemic therapy, alone or in combination. In recent years, immunotherapy strategies have revolutionized the treatment of many cancers, increasing the hope for GBM therapy. Regorafenib (Stivarga) is an inhibitor of several kinases involved in the mechanisms that regulate neoangiogenesis processes, through the inhibition vascular endothelial growth factor (VEGF) receptors and the modifications of the tumor microenvironment; specifically, Regorafenib binds an d stabilizes PSAT1 (phosphoserine aminotransferase 1). The dual regulatory mechanism underlying PSAT1-induced autophagy arrest accounts for the superior anti-GBM effect of Regorafenib compared with Temozolomide. Material and Methods 15 patients with documented disease progression after surgery followed by RT and TMZ were assigned to receive regorafenib (REG) 160 mg once daily for the first 3 weeks of each 4-week cycle. All patients received prior radiation therapy (RT) to a median dose of 60 Gy (range 40.05 -60). Median time to retreatment after prior RT was 16 months (range 14-33). Tumor volumes ranged from 81.7 cm3 to 422.4 cm3 (CTV) and from 112.7 cm3 to 422.4 cm3 (PTV).3 patients (20%) received concomitant reirradiation with a radiation dose of 37.5 Gy in 15 fractions of 2.5 Gy. Results the median follow-up was 9.5 months (range 5-22). The overall survival and the progression-free survival rates were 53,8 %, and 46,6 % respectively at 2 years. In 53% the sympto ms were stable. Only one patient developed late toxicity: acute pancreatitis (Grade I) regressed on interruption of Regorafenib. No other neurological deficits occurred during follow-up. At last follow up 60% of patients were alive. Conclusion we report our experience with Regorafenib, administered in patients with rapid progression after the end of postoperative radio chemotherapy treatment. Regorafenib might be a new potential treatment option for recurrent glioblastoma: it was well tolerated also in cases of combined treatment with reirradiation and appeared effective. Other studies will be necessary to evaluate and confirm the role of Regorafenib in glioblastoma patients and the potential effectiveness of the combined therapeutic strategy: Regorafenib-reirradiation. View on Web

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PL02.2.A Microglia-specific disruption of sialic acid-Siglec-9/E interactions. A novel immunotherapy against glioblastoma?

alexandrossfakianakis shared this article with you from Inoreader PL02.2.A Microglia-specific disruption of sialic acid-Siglec-9/E interactions. A novel immunotherapy against glioblastoma? via # Neuro-Oncology Current Issue Abstract Background Recently, 'don't eat me'-signals like CD47 have emerged as novel innate immune checkpoints, enabling cancer cells to evade clearance by phagocytes such as monocyte-derived macrophages (MdM) or microglia (MG). Here, we aim at defining the role of inhibitory Siglec-9 in human and its mouse homologue Siglec-E in MG-centered immunotherapy against GBM. Material and Methods We employed a CT-2A orthotopic GBM mouse model with MG specific (Sall1CreERT2 x Sigleceflox) and whole innate-compartment (Cx3cr1CreERT2 x Sigleceflox) spatio-temporal deletion of Siglece. We applied multi-color flow cytometry, transcriptomics and proteomics analysis to decipher the immune response upon Siglece knockout. Results TCGA RNA-sequencing data revealed a significant correlation between high expression of immunoinhibitory SIGLEC9 and poor survival in GBM patients (log-rank p = 0.02). Siglec-E blockade increased murine MG mediated GBM cell in vitro phagocytosis (normalized phagocytosis of 1.00 in isotype vs. 1.76 in anti-Siglec-E antibody, p < 0.001). In the MG specific spatio-temporal deletion of Siglece (Sall1CreERT2 xSigleceflox), we observed high MG-proliferation upon Siglec-E knockout (Ki-67+ MG 1 4.8% in Cre- vs. 34.9% in Cre+, p < 0.0001) accompanied by an enhanced microglial GBM-cell uptake (5.6% in Cre- vs. 12.3% in Cre+, p < 0.001). By extending the Siglece knockout to the MdM compartment in our glioma mouse model (Cx3cr1CreERT2 x Sigleceflox) we observed a significantly prolonged survival in the Cx3cr1Cre+ population (21d in Cre- vs. 27d post-tumor injection in Cre+, p = 0.018), which could be further promoted by combining Siglece knockout with CD47 blockade (30d post-tumor injection in Cre+ + anti-CD47). Unbiased proteomics analysis revealed increased antigen processing and presentation capabilities of Siglece knockout MdMs which was confirmed by ex-vivo OT-1 cross-presentation assays. This bridging of innate and adaptive responses with increased T cell priming upon MdM Siglece knockout was further promoted by addition of anti-PD1 antibody to the combined Siglece knockout and anti-CD47 treatment arm. Animals harboring CT-2A tumors, exhibited a sustained survival benefit under the triple therapy, with 23% of animals experiencing long-term remission, even after tumor re-challenge into the contra-lateral hemisphere. By genetically targeting sialic acids, the ligand for Siglec receptors, on CT-2A cells (GNE-KO), we observed a strong innate and adaptive immune response with increased GBM-cell phagocytosis by MG and MdMs and less exhausted tumor-infiltrating CD8+ T-cells (14.8% in WT vs. 5.9% in GNE-KO, p = 0.003). Conclusion These data identify the sialic-acid-Sigl ec-E pathway as an anti-phagocytic signal in a pre-clinical GBM model, and demonstrate its therapeutic potential in GBM immunotherapy. View on Web

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