P18.11.A Active beam scanning proton therapy for large skull base benign meningiomas: long-term results

alexandrossfakianakis shared this article with you from Inoreader P18.11.A Active beam scanning proton therapy for large skull base benign meningiomas: long-term results via # Neuro-Oncology Current Issue Abstract Purpose To report long-term results of active beam scanning proton therapy (PT) for large skull base benign meningiomas Material and Methods Eighty-two patients (pts) with large skull base meningiomas were treated with PT between April 2015 and December 2021. Median age was 62 years (range, 48-82) while KPS ranged between 60 and 100 (median 90); 60 were female (73%), and 22 were male (27%). Thirty-two pts (39%) had histologically proven World Health Organization (WHO) Grade I tumors. In remaining pts diagnosis was based on the typical imaging appearance of benign meningioma. All patients received PT for residual, progressive or non-operable lesions. Newly diagnosed tumors received total dose of 50 GyRBE (RBE: relative biologic effectiveness) while progressing meningiomas 54 GyRBE. All the treatments were delivered at 2 GyRBE per fraction. All pts were treated with active beam scanning PT using 3 fields with single field optimiz ation technique. Treatment planning was based on morphological magnetic resonance imaging (MRI) with contrast enhancement medium administration. All pts received also 68-Ga-DOTATOC-PET. Gross tumor volume ranged from 21 to 64 cc. Toxicity was assessed according to Common Terminology Criteria for Adverse Events version 4.0. Median follow-up time was 40 months (range, 3-83). Results All pts completed the treatment without breaks. Registered acute side effects include grade 1 (19%) and grade 2 (8%) skin erythema, grade 1 (5%) and grade 2 (5%) alopecia, grade 1 (40%) fatigue, grade 1 (5%) and grade 2 (10%) conjunctivitis, grade 1 (10%) pain, grade 1 (5%) blurred vision, grade 1 (10%) headache, and grade 2 (5%) skin hyperpigmentation. One pts (1%) experienced grade 3 pain. There were no further grade 3 or higher acute toxicities. Registered late side effects include grade 1 (2%) and grade 2 (5%) alopecia, grade 1 (21%) fatigue, grade 1 (5%) and grade 2 (5%) headache, grade 1 (6% ) dizziness, grade 1 (3%) blurred vision, grade 1 (3%) and grade 2 (6%) pain, grade 1 (2%) dry eye, and grade 1 (5%) skin hyperpigmentation. Two pts (2%) experienced grade 3 pain. Two further pts (2%) experienced grade 3 optic neuropathy. There were no further grade 3 or higher late toxicities. During follow-up one pts (1%) with cavernous sinus meningioma experienced complete obstruction of intracavernous carotid artery with mild transient symptoms that resolved in few days and brain tissue ischemia detected at MRI (grade 2). Before irradiation this pts already had a meningioma-related near-complete obstruction of the intracavernous carotid artery and received a vascular surgery evaluation. Currently, absolute tumor control is 99%. Moreover, relief of symptoms recorded before irradiation occurred in 40% of pts. Conclusion PT is safe and effective treatment for pts with large skull base benign meningiomas. View on Web

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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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P11.52.A Peripheral neuropathies after BRAF and/or MEK inhibitors treatment: a pharmacovigilance study

alexandrossfakianakis shared this article with you from Inoreader P11.52.A Peripheral neuropathies after BRAF and/or MEK inhibitors treatment: a pharmacovigilance study via # Neuro-Oncology Current Issue Abstract Background BRAF (BRAFi) and MEK inhibitors (MEKi) demonstrated significant efficacy in the treatment of BRAF-activated tumours, firstly melanoma. Nevertheless, they are not devoid of adverse events. Sparse reports in the literature suggest the potential occurrence of peripheral neuropathies (PN) under BRAFi/MEKi treatment, but their characteristics remain poorly defined. We aimed to characterize the clinical phenotypes of PN occurring under BRAFi/MEKi treatment using a national pharmacovigilance database. Material and Methods We queried the French pharmacovigilance database for all cases of PN toxicity attributed to at least one BRAFi or MEKi compound. Only cases with a least symptoms description and nerve conduction studies (NCS) conclusion were included. Results Sixteen cases of PN occurred in 15 patients were identified. All patients had underlying melanoma. Two main phenotypes were seen. Six patients (dabrafenib-tr ametinib, n=3; vemurafenib, n=2; vemurafenib-cobimetinib, n=1) presented a length-dependent axonal polyneuropathy: symptoms were mostly sensory at lower limbs; NCS disclosed an axonal neuropathy; management and outcome were variable. Nine patients (dabrafenib-trametinib, n=5, encorafenib-binimetinib, n=3, and vemurafenib-cobimetinib, n=1) developed a demyelinating polyradiculoneuropathy: symptoms affected the four limbs and included hypoesthesia, weakness, and ataxia; cranial nerves were involved in four; NCS showed predominantly demyelinating features; most patients received intravenous immunoglobulins (n=6) or glucocorticoids (n=5), but the outcome was variable; one patient was rechallenged with a different BRAFi/MEKi with a rapid relapse. Conclusion Patients under treatment with BRAFi/MEKi may develop treatment-induced PN. Two main phenotypes are seen: a symmetric, axonal, length-dependent polyneuropathy, and a demyelinating polyradiculoneuropathy. View on Web

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P05.03.B Application of rapid cytology in intraoperative diagnosis of primary central nervous system lymphoma

alexandrossfakianakis shared this article with you from Inoreader P05.03.B Application of rapid cytology in intraoperative diagnosis of primary central nervous system lymphoma via # Neuro-Oncology Current Issue Abstract Background To assesment the value of rapid cytological diagnosis in primary central nervous system lymphoma (PCNSL) surgery. Material and Methods A total of 213 PCNSL specimens from the First Affiliated Hospital of Fujian Medical University between 2012 to 2022 were included, 1-2mm3 was taken from the tissues diagnosed for intraoperative pathology and made into cell smears, rapid cytological diagnosis was performed after 95% ethanol fixation and H&E staining, most of the remaining tissues were diagnosed by frozen section. With the results of paraffin section pathological diagnosis as the control standard, compared the accuracy of rapid cytology and frozen tissue section and their combined diagnosis. Results Cytological smears can reveal microscopic structures within the cells under a microscope, furthermore, it can avoid the formation of artifacts or deformation of cells when frozen due to excessive wate r in brain tissue. Compared with paraffin section pathological diagnosis, the diagnostic accuracy of rapid cytology was 151cases (70.89%) , that of frozen tissue section was 175 cases (82.16%) , and that of the combination of the two methods was 187 cases (87.79%) . There were 26 cases (12.21%) in which neither method could give a definite conclusion intraoperatively and only depended on the results of paraffin tissue sections. Conclusion Rapid cytology alone is less accurate in diagnosing PCNSL than frozen sections alone. However, the combination of the two diagnosis can improve the accuracy of intraoperative diagnosis of PCNSL and correct some errors that may occur when only relying on frozen section diagnosis. It is especially suitable for stereotactic biopsy surgery or cases with very little tissue, as well as primary medical units without frozen section machine and other equipment. View on Web

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P11.29.B Risk factors associated with the presence of brain metastasis at the moment of diagnosis in non-small cell lung cancer patients. Retrospective case series

alexandrossfakianakis shared this article with you from Inoreader P11.29.B Risk factors associated with the presence of brain metastasis at the moment of diagnosis in non-small cell lung cancer patients. Retrospective case series via # Neuro-Oncology Current Issue Abstract Background Lung cancer is the second most frequent neoplasm worldwide and the leading cause of cancer death in both sexes. Furthermore, it is the most common origin of brain metastases. The aim of this study is to identify clinical, histological, and molecular variables associated with a higher risk of presenting brain metastases at the moment of diagnosis in patients with lung cancer. Material and Methods A single-center retrospective case series analysis of patients with a new diagnosis of lung cancer (from January 2015 to December 2018) was performed. A total of 723 total patients with a new diagnosis of non-small cell lung cancer (NSCLC) were identified. Only patients with a brain imaging study at the time of diagnosis were included in the analysis. Non-parametric statistical tests were used to compare patients with or without metastases at the moment of diagnosis. A uni- and multivariate analysis were performed to identify risk factors associated with the presence of brain metastases at NSCLC diagnosis. Statistical significance was considered when p<0.05. Results We included 135 patients with a new diagnosis of lung cancer and with brain imaging study at the time of diagnosis (mean age at diagnosis of 64.69 years [SD= 10.34]; 71.9% men). The most common histology was adenocarcinoma (67.1%) followed by squamous carcinoma (25.2%). Brain metastases were present in 40% of patients at diagnosis. No significant differences in clinical, histological and molecular variables was identified between patients with or without brain metastases. In any case, as expected, the survival analysis showed that brain metastasis at diagnosis was associated with a worse overall survival (Log-Rank test, p<0.01).The univariate analysis showed that presenting neurological symptoms (OR=19.5, p<0.0001 CI [7.895-47.65]), histology of adenocarcinoma (OR= 2.113, p<0.014 CI [1.160-3.849]) and the presence of vis ceral metastases (OR= 14.444, p<0.0001 CI [6.161-33.86]) were associated to the presence of brain metastases at diagnosis. The presence of metastases limited to the thorax (OR= 0.019, p<0.001 CI [0.003-0.146] was associated to be free of brain metastasis at NSCLC diagnosis. However, only neurological symptoms (OR= 20.290, p<0.0001 CI [4.953-83.118]), presenting visceral metastases (OR= 4.451, p<0.010 CI [1.458-13.777]) and/or metastases limited to the thorax (OR= 0.066, p<0.024 CI [0.006-0.010]) reached statistical significance in the multivariate analysis. Conclusion Neurological symptoms and the presence of visceral metastases are independent predictors or presenting brain metastasis at the moment of diagnosis in lung cancer patients. On the other hand, the presence of lung cancer disease confined in the thoracic cavity is associated with a lower risk to present brain metastasis 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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P02.01.B The telomere maintenance mechanism spectrum and its dynamics in gliomas

alexandrossfakianakis shared this article with you from Inoreader P02.01.B The telomere maintenance mechanism spectrum and its dynamics in gliomas via # Neuro-Oncology Current Issue Abstract The activation of the telomere maintenance mechanism (TMM) is one of the critical drivers of cancer cell immortality. In gliomas, TERT expression and TERT promoter mutation are considered to reliably indicate telomerase activation, while ATRX mutation indicates alternative lengthening of telomeres (ALT). However, these relationships have not been extensively validated in tumor tissues. Here, we show through the direct measurement of telomerase activity and ALT in a large set of glioma samples that the TMM in glioma cannot be defined in the dichotomy of telomerase activity and ALT, regardless of TERT expression, TERT promoter mutation and ATRX mutation. Moreover, we observed that a considerable proportion of gli omas lack both telomerase activity and ALT (Neither group). And this Neither group exhibited evidence of slow growth potential. From a set of longitudinal samples from a separate cohort of glioma patients, we discovered that the TMM is not fixed but changes with glioma progression. Collectively, these results suggest that the TMM is a dynamic entity and that reflects the plasticity of the oncogenic biological status of tumor cells and that the TMM should be defined by the direct measurement of telomerase enzyme activity and evidence of ALT. 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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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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