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Papers by Gorm Von Oettingen

Anesthesiology, 2020

Background Studies in anesthetized patients suggest that phenylephrine reduces regional cerebral ... more Background Studies in anesthetized patients suggest that phenylephrine reduces regional cerebral oxygen saturation compared with ephedrine. The present study aimed to quantify the effects of phenylephrine and ephedrine on cerebral blood flow and cerebral metabolic rate of oxygen in brain tumor patients. The authors hypothesized that phenylephrine reduces cerebral metabolic rate of oxygen in selected brain regions compared with ephedrine. Methods In this double-blinded, randomized clinical trial, 24 anesthetized patients with brain tumors were randomly assigned to ephedrine or phenylephrine treatment. Positron emission tomography measurements of cerebral blood flow and cerebral metabolic rate of oxygen in peritumoral and normal contralateral regions were performed before and during vasopressor infusion. The primary endpoint was between-group difference in cerebral metabolic rate of oxygen. Secondary endpoints included changes in cerebral blood flow, oxygen extraction fraction, and re...

SSRN Electronic Journal, 2021

Radiotherapy and Oncology, 2014

Acta neurologica Scandinavica. Supplementum, 1996

Radiotherapy and Oncology, 2020

Neuro-Oncology Advances, 2020

Background Preclinical studies suggest that skull remodeling surgery (SR-surgery) increases the d... more Background Preclinical studies suggest that skull remodeling surgery (SR-surgery) increases the dose of tumor treating fields (TTFields) in glioblastoma (GBM) and prevents wasteful current shunting through the skin. SR-surgery introduces minor skull defects to focus the cancer-inhibiting currents toward the tumor and increase the treatment dose. This study aimed to test the safety and feasibility of this concept in a phase I setting. Methods Fifteen adult patients with the first recurrence of GBM were treated with personalized SR-surgery, TTFields, and physician’s choice oncological therapy. The primary endpoint was toxicity and secondary endpoints included standard efficacy outcomes. Results SR-surgery resulted in a mean skull defect area of 10.6 cm2 producing a median TTFields enhancement of 32% (range 25–59%). The median TTFields treatment duration was 6.8 months and the median compliance rate 90%. Patients received either bevacizumab, bevacizumab/irinotecan, or temozolomide rech...

Neuro-oncology, 2017

BACKGROUND: Bortezomib is a slowly reversible proteasome inhibitor. Anti-tumor activity of bortez... more BACKGROUND: Bortezomib is a slowly reversible proteasome inhibitor. Anti-tumor activity of bortezomib has shown efficacy towards GBM cell lines. Study has also demonstrated that the bortezomib is a potential caspase dependent apoptosis inducer in GBM cells. Our phase II study is to assess the safety and efficacy of bortezomib in combination with temozolomide and radiation therapy (RT) followed by bortezomib and temozolomide for up to 24 cycles of adjuvant therapy for the upfront treatment of patients with newly-diagnosed GBM. PATIENTS AND METHODS: Twenty-four patients with newly-diagnosed GBM from UCLA or Columbia, were enrolled in our study. All patients received standard external beam regional RT, concurrent daily temozolomide for 6 weeks, and bortezomib was given at 1.3 mg/m 2 during concomitant chemoradiation therapy and adjuvant chemotherapy for up to 24 cycles or until tumor progression. RESULTS AND CONCLUSION: No unexpected adverse events occurred due to the addition of bortezomib. In comparison to historical data, efficacy analysis showed a comparable median progression free survival (PFS) of 6.2 months (95% CI, 3.7-8.8) and median overall survival (OS) of 19.1 months (95% CI, 6.7-31.4), but have increased PFS rate beyond 18 months (25% at 18, 25% at 24 and 17% at 30 months), and increased OS rate beyond 12 months (88% at 12, 50% at 24, 34% at 36 throughout 60 months). MGMT methylated patients appeared to derive enhanced benefits. Median PFS was 24.7 months (95% CI 8.5-41.0) in 10 methylated and 5.1 months (95% CI 3.9-6.2) in 13 unmethylated patients. The estimated median OS was 61 months in the methylated (the upper bound of 95% CI could not be calculated) and 16.4 months (95% CI 11.8-21.0) in the unmethylated patients. Our methylated patients outperformed historical control methylated patients. Cases are limited in number; further clinical investigation is warranted in a larger cohort of patients.

BMJ open, Jan 17, 2017

During brain tumour surgery, vasopressor drugs are commonly administered to increase mean arteria... more During brain tumour surgery, vasopressor drugs are commonly administered to increase mean arterial blood pressure with the aim of maintaining sufficient cerebral perfusion pressure. Studies of the commonly used vasopressors show that brain oxygen saturation is reduced after phenylephrine administration, but unaltered by ephedrine administration. These findings may be explained by different effects of phenylephrine and ephedrine on the cerebral microcirculation, in particular the capillary transit-time heterogeneity, which determines oxygen extraction efficacy. We hypothesised that phenylephrine is associated with an increase in capillary transit-time heterogeneity and a reduction in cerebral metabolic rate of oxygen compared with ephedrine. Using MRI and positron emission tomography (PET) as measurements in anaesthetised patients with brain tumours, this study will examine whether phenylephrine administration elevates capillary transit-time heterogeneity more than ephedrine, thereby...

The Keio journal of medicine, 2000

Measurements of rCBF by the Xe/CT method are based on the assumption of identity between the end-... more Measurements of rCBF by the Xe/CT method are based on the assumption of identity between the end-tidal xenon curve which is applied as input function, and the arterial xenon curve being the true input function to the brain. In this study corresponding end-tidal and arterial xenon curves were measured in an experimental animal model (part 1) and in 5 patients with traumatic brain injury (part 2) and used for rCBF calculation. In both studies rCBF was underestimated by using the end-tidal xenon concentration curve as brain input function. In part 1 rCBF underestimation was depended on pulmonary gas exchange; high or low levels of rCBF; tissue type; and xenon inhalation protocols. In part 2 the mean rCBF underestimation was 18.8 +/- 8.3%. In conclusion, non-invasive estimate of the input function should be considered as a source of error when defining quantitative blood flow values e.g. the flow thresholds of ischaemic infarction.

Acta Oncologica, 2014

Background. Stereotactic radiation therapy (SRT) of brain metastases is used with good effect aro... more Background. Stereotactic radiation therapy (SRT) of brain metastases is used with good effect around the world, but no consensus exists regarding which prognostic factors that are related to favourable or unfavourable prognosis after the treatment. A better defi nition of these factors will ensure a more precise application of the treatment. Material and methods. A consecutive cohort of the 198 patients treated for brain metastases with SRT without concurrent whole-brain radiation therapy at our department from 2001 to 2012 was retrospectively analysed. Results. Median survival was seven months and median time to clinical cerebral progression was eight months. The multivariate analysis revealed age Ն 65 years, Performance Status Ն 2, extracranial metastases and size of metastasis Ͼ 20 mm as independent prognostic factors related to shorter survival. No factors were independently related to clinical cerebral progression. Conclusion. We identifi ed four prognostic factors related to survival after SRT for brain metastases. The grouping of patients by these factors is useful to determine the level of treatment. We discourage the delivery of SRT to patients with 3-4 unfavourable prognostic factors because of the very short median survival of two months.

Journal of Stroke and Cerebrovascular Diseases, 1997

Radiotherapy and Oncology, 2021

Blood

§ s hared first authorship; §§ s hared last authorship Primary Central Nervous System Lymphoma (P... more § s hared first authorship; §§ s hared last authorship Primary Central Nervous System Lymphoma (PCNSL) is a rare and aggressive non-Hodgkin lymphoma with limited treatment options and severe prognosis. It may display copy number abnormalities of the 9p24.1 locus harboring the programmed cell death protein ligand 1 (PD-L1) gene. Moreover, tumor lesions often overexpress programmed cell death protein 1 (PD-1) as well as its ligands (PD-L1/PD-L2). Soluble forms of these molecules have been demonstrated in serum and plasma, though the biological and clinical significance of these soluble checkpoint proteins is yet unclear. Furthermore, their presence in the cerebrospinal fluid (CSF), particularly in malignant diseases, is largely unexplored. Thus, the aim of our study was to measure the occurrence of soluble PD-1 (sPD-1) in the CSF of PCNSL patients. We measured sPD-1 levels in pretherapeutic plasma and CSF samples from 11 patients with histopathologically confirmed PCNSL of diffuse large B-cell type (DLBCL) and five patients in which the histopathological examination did not confirm the initial clinical and imaging-based suspicion of PCNSL diagnosis (non-PCNSL). All blood and CSF samples were obtained prior to neurosurgical biopsy. Of these five patients, four had reactive non-malignant lesions and one a glioblastoma. Six CSF samples routinely screened for non-malignant neurological disease (e.g. sclerosis) were included as an additional non-PCNSL control group (neuro-screen samples). All samples were handled identically prior to analysis. Soluble PD-1 was measured using an in-house time-resolved immunofluorometric assay (TRIFMA) as previously reported by our group (Mortensen JB et al. Eur J Haematol. 2021 Jul;107:81-91). All samples were analyzed in duplicates. The TRIFMA was validated for freeze/thaw interference and recovery. We found that pretherapeutic CSF sPD-1 levels in PCNSL patients were approximately 10 to 30-fold higher than those of non-PCNSL and neuro-screen patients (p<0,001). The median CSF sPD-1 level for PCNSL was 628 pg/mL, while the corresponding values for the non-PCNSL and neuro-screen subgroups were 48 pg/mL and 19 pg/mL, respectively. Fig. 1a shows the sPD-1 values measured in the three different subsets (PCNSL, non-PCNSL, neuro-screen) of the study cohort. Three PCSNL patients had particularly high sPD-1 values (range: 1642-2194 pg/mL) in their pretherapeutic CSF samples. Interestingly, these three patients all displayed 'high-risk' molecular features, i.e., one case of double-overexpression of bcl-6 and c-Myc and the only two cases of triple-overexpression of bcl-2, bcl-6 and c-Myc. In all 11 PCNSL patients, the DLBCL histology had an activated B-cell like (ABC)/non-germinal center B-cell like (non-GCB) signature. Plasma samples were only available for the PCNSL and non-PCNSL subsets. The median plasma sPD-1 value was 142 pg/mL and 124 pg/mL, respectively. As opposed to non-PCNSL, the CSF sPD-1 levels of PCNSL patients were higher than the paired plasma values (p<0.001; Fig.1b). TRIFMA based measurement of sPD-L1/2 in all available CSF samples and genomic analyses of pretherapeutic PCNSL tissue biopsies are ongoing. At the time of analysis, the median follow-up of the PCNSL cohort was 17 months (range: 1-47) with three deaths observed at 1, 2 and 4 months, respectively. Among the remaining eight patients, six are in continuous 1st complete remission (CR) and two in 2nd CR. Of the six patients in 1st CR, four underwent consolidation with upfront autologous transplant. So far, no significant correlation between CSF sPD-1 and survival has been observed. Despite the limited size of our cohort, we demonstrated that sPD-1 is present and measurable in the CSF of previously untreated PCNSL patients. Moreover, we observed that sPD-1 levels in the pretherapeutic CSF samples from PCNSL were significantly higher than those measured in the non-PCNSL and neuro-screen samples. The PCNSL patients with the most adverse histological features were also the ones with the highest sPD-1 levels in the pretherapeutic CSF. Confirmation of these findings in a larger independent cohort as well as sequential measurements obtained during the course of the disease are warranted. If confirmed, our observations may help to evaluate the usefulness of CSF sPD-1 measurements with regard to disease monitoring as well as checkpoint inhibition strategies in PCNSL. Figure 1 Figure 1. Disclosures Pulczynski: Investigator of a clinical trial (Nordic Lymphoma Group NLG- LBC7(Polar Bear) EudraCT No 2018- 0038 funded by Roche: Research Funding.

Neuro-Oncology

INTRODUCTION High grade neuroepithelial tumor with BCOR exon 15 internal tandem duplication (HGNE... more INTRODUCTION High grade neuroepithelial tumor with BCOR exon 15 internal tandem duplication (HGNET BCOR) is a recently described tumor entity of the central nervous system (CNS) with a distinct methylation profile and characteristic genetic alteration. We report the outcome of two cases after 1st line multimodality therapy. MATERIAL AND METHOD A 7 year old girl with a ventricular tumour and a 6 year old boy with a tumour in the occipital region with infiltration of the transverse and sigmoid sinus were both diagnosed based on histology and methylation with HGNET-BCOR. No spinal or liquor dissemination were found at diagnosis in both cases. Treatment consisted of radical resection of the tumour. In the case of the lesion with sinus infiltration residual tumour in the vessel could not be removed. Both children were postoperatively treated with radiotherapy (craniospinal 36 Gy and boost to 54 Gy), concomitant Vincristin and adjuvant Cisplatin, Lomustine and Vincristine. RESULTS The gir...

Neuro-Oncology

INTRODUCTION Intracranial malignant germ cell tumours (iGCT) are rare brain tumours mainly diagno... more INTRODUCTION Intracranial malignant germ cell tumours (iGCT) are rare brain tumours mainly diagnosed in children and younger adults. MATERIAL AND METHODS A retrospective analysis was performed by chart review of patients treated for iGCT in the northern and central region of Denmark. Teratoma only patients were not included in the study. RESULTS 20 patients with iGCT were diagnosed from 2008–2019 in Western Denmark. The cumulative incidence was 1.05 per 100.000. The yearly incidence was 0.1 per 100.000. Mean age at diagnosis was 18 years (range 8–36 years), 17 were males and 3 were females. 13 patients presented with germinoma and 7 patients with non germinomateous germ cell tumours (NGGCT). Three patients had disseminated disease, two with germinoma and one with NGGCT. All patients had received radiotherapy and 18 patients were treated with multidrug chemotherapy including platinum and etoposide before irradiation. Two patients experienced recurrent disease, both non disseminated a...

Radiotherapy and Oncology

Anesthesiology, 2020

Background Studies in anesthetized patients suggest that phenylephrine reduces regional cerebral ... more Background Studies in anesthetized patients suggest that phenylephrine reduces regional cerebral oxygen saturation compared with ephedrine. The present study aimed to quantify the effects of phenylephrine and ephedrine on cerebral blood flow and cerebral metabolic rate of oxygen in brain tumor patients. The authors hypothesized that phenylephrine reduces cerebral metabolic rate of oxygen in selected brain regions compared with ephedrine. Methods In this double-blinded, randomized clinical trial, 24 anesthetized patients with brain tumors were randomly assigned to ephedrine or phenylephrine treatment. Positron emission tomography measurements of cerebral blood flow and cerebral metabolic rate of oxygen in peritumoral and normal contralateral regions were performed before and during vasopressor infusion. The primary endpoint was between-group difference in cerebral metabolic rate of oxygen. Secondary endpoints included changes in cerebral blood flow, oxygen extraction fraction, and re...

SSRN Electronic Journal, 2021

Radiotherapy and Oncology, 2014

Acta neurologica Scandinavica. Supplementum, 1996

Radiotherapy and Oncology, 2020

Neuro-Oncology Advances, 2020

Background Preclinical studies suggest that skull remodeling surgery (SR-surgery) increases the d... more Background Preclinical studies suggest that skull remodeling surgery (SR-surgery) increases the dose of tumor treating fields (TTFields) in glioblastoma (GBM) and prevents wasteful current shunting through the skin. SR-surgery introduces minor skull defects to focus the cancer-inhibiting currents toward the tumor and increase the treatment dose. This study aimed to test the safety and feasibility of this concept in a phase I setting. Methods Fifteen adult patients with the first recurrence of GBM were treated with personalized SR-surgery, TTFields, and physician’s choice oncological therapy. The primary endpoint was toxicity and secondary endpoints included standard efficacy outcomes. Results SR-surgery resulted in a mean skull defect area of 10.6 cm2 producing a median TTFields enhancement of 32% (range 25–59%). The median TTFields treatment duration was 6.8 months and the median compliance rate 90%. Patients received either bevacizumab, bevacizumab/irinotecan, or temozolomide rech...

Neuro-oncology, 2017

BACKGROUND: Bortezomib is a slowly reversible proteasome inhibitor. Anti-tumor activity of bortez... more BACKGROUND: Bortezomib is a slowly reversible proteasome inhibitor. Anti-tumor activity of bortezomib has shown efficacy towards GBM cell lines. Study has also demonstrated that the bortezomib is a potential caspase dependent apoptosis inducer in GBM cells. Our phase II study is to assess the safety and efficacy of bortezomib in combination with temozolomide and radiation therapy (RT) followed by bortezomib and temozolomide for up to 24 cycles of adjuvant therapy for the upfront treatment of patients with newly-diagnosed GBM. PATIENTS AND METHODS: Twenty-four patients with newly-diagnosed GBM from UCLA or Columbia, were enrolled in our study. All patients received standard external beam regional RT, concurrent daily temozolomide for 6 weeks, and bortezomib was given at 1.3 mg/m 2 during concomitant chemoradiation therapy and adjuvant chemotherapy for up to 24 cycles or until tumor progression. RESULTS AND CONCLUSION: No unexpected adverse events occurred due to the addition of bortezomib. In comparison to historical data, efficacy analysis showed a comparable median progression free survival (PFS) of 6.2 months (95% CI, 3.7-8.8) and median overall survival (OS) of 19.1 months (95% CI, 6.7-31.4), but have increased PFS rate beyond 18 months (25% at 18, 25% at 24 and 17% at 30 months), and increased OS rate beyond 12 months (88% at 12, 50% at 24, 34% at 36 throughout 60 months). MGMT methylated patients appeared to derive enhanced benefits. Median PFS was 24.7 months (95% CI 8.5-41.0) in 10 methylated and 5.1 months (95% CI 3.9-6.2) in 13 unmethylated patients. The estimated median OS was 61 months in the methylated (the upper bound of 95% CI could not be calculated) and 16.4 months (95% CI 11.8-21.0) in the unmethylated patients. Our methylated patients outperformed historical control methylated patients. Cases are limited in number; further clinical investigation is warranted in a larger cohort of patients.

BMJ open, Jan 17, 2017

During brain tumour surgery, vasopressor drugs are commonly administered to increase mean arteria... more During brain tumour surgery, vasopressor drugs are commonly administered to increase mean arterial blood pressure with the aim of maintaining sufficient cerebral perfusion pressure. Studies of the commonly used vasopressors show that brain oxygen saturation is reduced after phenylephrine administration, but unaltered by ephedrine administration. These findings may be explained by different effects of phenylephrine and ephedrine on the cerebral microcirculation, in particular the capillary transit-time heterogeneity, which determines oxygen extraction efficacy. We hypothesised that phenylephrine is associated with an increase in capillary transit-time heterogeneity and a reduction in cerebral metabolic rate of oxygen compared with ephedrine. Using MRI and positron emission tomography (PET) as measurements in anaesthetised patients with brain tumours, this study will examine whether phenylephrine administration elevates capillary transit-time heterogeneity more than ephedrine, thereby...

The Keio journal of medicine, 2000

Measurements of rCBF by the Xe/CT method are based on the assumption of identity between the end-... more Measurements of rCBF by the Xe/CT method are based on the assumption of identity between the end-tidal xenon curve which is applied as input function, and the arterial xenon curve being the true input function to the brain. In this study corresponding end-tidal and arterial xenon curves were measured in an experimental animal model (part 1) and in 5 patients with traumatic brain injury (part 2) and used for rCBF calculation. In both studies rCBF was underestimated by using the end-tidal xenon concentration curve as brain input function. In part 1 rCBF underestimation was depended on pulmonary gas exchange; high or low levels of rCBF; tissue type; and xenon inhalation protocols. In part 2 the mean rCBF underestimation was 18.8 +/- 8.3%. In conclusion, non-invasive estimate of the input function should be considered as a source of error when defining quantitative blood flow values e.g. the flow thresholds of ischaemic infarction.

Acta Oncologica, 2014

Background. Stereotactic radiation therapy (SRT) of brain metastases is used with good effect aro... more Background. Stereotactic radiation therapy (SRT) of brain metastases is used with good effect around the world, but no consensus exists regarding which prognostic factors that are related to favourable or unfavourable prognosis after the treatment. A better defi nition of these factors will ensure a more precise application of the treatment. Material and methods. A consecutive cohort of the 198 patients treated for brain metastases with SRT without concurrent whole-brain radiation therapy at our department from 2001 to 2012 was retrospectively analysed. Results. Median survival was seven months and median time to clinical cerebral progression was eight months. The multivariate analysis revealed age Ն 65 years, Performance Status Ն 2, extracranial metastases and size of metastasis Ͼ 20 mm as independent prognostic factors related to shorter survival. No factors were independently related to clinical cerebral progression. Conclusion. We identifi ed four prognostic factors related to survival after SRT for brain metastases. The grouping of patients by these factors is useful to determine the level of treatment. We discourage the delivery of SRT to patients with 3-4 unfavourable prognostic factors because of the very short median survival of two months.

Journal of Stroke and Cerebrovascular Diseases, 1997

Radiotherapy and Oncology, 2021

Blood

§ s hared first authorship; §§ s hared last authorship Primary Central Nervous System Lymphoma (P... more § s hared first authorship; §§ s hared last authorship Primary Central Nervous System Lymphoma (PCNSL) is a rare and aggressive non-Hodgkin lymphoma with limited treatment options and severe prognosis. It may display copy number abnormalities of the 9p24.1 locus harboring the programmed cell death protein ligand 1 (PD-L1) gene. Moreover, tumor lesions often overexpress programmed cell death protein 1 (PD-1) as well as its ligands (PD-L1/PD-L2). Soluble forms of these molecules have been demonstrated in serum and plasma, though the biological and clinical significance of these soluble checkpoint proteins is yet unclear. Furthermore, their presence in the cerebrospinal fluid (CSF), particularly in malignant diseases, is largely unexplored. Thus, the aim of our study was to measure the occurrence of soluble PD-1 (sPD-1) in the CSF of PCNSL patients. We measured sPD-1 levels in pretherapeutic plasma and CSF samples from 11 patients with histopathologically confirmed PCNSL of diffuse large B-cell type (DLBCL) and five patients in which the histopathological examination did not confirm the initial clinical and imaging-based suspicion of PCNSL diagnosis (non-PCNSL). All blood and CSF samples were obtained prior to neurosurgical biopsy. Of these five patients, four had reactive non-malignant lesions and one a glioblastoma. Six CSF samples routinely screened for non-malignant neurological disease (e.g. sclerosis) were included as an additional non-PCNSL control group (neuro-screen samples). All samples were handled identically prior to analysis. Soluble PD-1 was measured using an in-house time-resolved immunofluorometric assay (TRIFMA) as previously reported by our group (Mortensen JB et al. Eur J Haematol. 2021 Jul;107:81-91). All samples were analyzed in duplicates. The TRIFMA was validated for freeze/thaw interference and recovery. We found that pretherapeutic CSF sPD-1 levels in PCNSL patients were approximately 10 to 30-fold higher than those of non-PCNSL and neuro-screen patients (p<0,001). The median CSF sPD-1 level for PCNSL was 628 pg/mL, while the corresponding values for the non-PCNSL and neuro-screen subgroups were 48 pg/mL and 19 pg/mL, respectively. Fig. 1a shows the sPD-1 values measured in the three different subsets (PCNSL, non-PCNSL, neuro-screen) of the study cohort. Three PCSNL patients had particularly high sPD-1 values (range: 1642-2194 pg/mL) in their pretherapeutic CSF samples. Interestingly, these three patients all displayed 'high-risk' molecular features, i.e., one case of double-overexpression of bcl-6 and c-Myc and the only two cases of triple-overexpression of bcl-2, bcl-6 and c-Myc. In all 11 PCNSL patients, the DLBCL histology had an activated B-cell like (ABC)/non-germinal center B-cell like (non-GCB) signature. Plasma samples were only available for the PCNSL and non-PCNSL subsets. The median plasma sPD-1 value was 142 pg/mL and 124 pg/mL, respectively. As opposed to non-PCNSL, the CSF sPD-1 levels of PCNSL patients were higher than the paired plasma values (p<0.001; Fig.1b). TRIFMA based measurement of sPD-L1/2 in all available CSF samples and genomic analyses of pretherapeutic PCNSL tissue biopsies are ongoing. At the time of analysis, the median follow-up of the PCNSL cohort was 17 months (range: 1-47) with three deaths observed at 1, 2 and 4 months, respectively. Among the remaining eight patients, six are in continuous 1st complete remission (CR) and two in 2nd CR. Of the six patients in 1st CR, four underwent consolidation with upfront autologous transplant. So far, no significant correlation between CSF sPD-1 and survival has been observed. Despite the limited size of our cohort, we demonstrated that sPD-1 is present and measurable in the CSF of previously untreated PCNSL patients. Moreover, we observed that sPD-1 levels in the pretherapeutic CSF samples from PCNSL were significantly higher than those measured in the non-PCNSL and neuro-screen samples. The PCNSL patients with the most adverse histological features were also the ones with the highest sPD-1 levels in the pretherapeutic CSF. Confirmation of these findings in a larger independent cohort as well as sequential measurements obtained during the course of the disease are warranted. If confirmed, our observations may help to evaluate the usefulness of CSF sPD-1 measurements with regard to disease monitoring as well as checkpoint inhibition strategies in PCNSL. Figure 1 Figure 1. Disclosures Pulczynski: Investigator of a clinical trial (Nordic Lymphoma Group NLG- LBC7(Polar Bear) EudraCT No 2018- 0038 funded by Roche: Research Funding.

Neuro-Oncology

INTRODUCTION High grade neuroepithelial tumor with BCOR exon 15 internal tandem duplication (HGNE... more INTRODUCTION High grade neuroepithelial tumor with BCOR exon 15 internal tandem duplication (HGNET BCOR) is a recently described tumor entity of the central nervous system (CNS) with a distinct methylation profile and characteristic genetic alteration. We report the outcome of two cases after 1st line multimodality therapy. MATERIAL AND METHOD A 7 year old girl with a ventricular tumour and a 6 year old boy with a tumour in the occipital region with infiltration of the transverse and sigmoid sinus were both diagnosed based on histology and methylation with HGNET-BCOR. No spinal or liquor dissemination were found at diagnosis in both cases. Treatment consisted of radical resection of the tumour. In the case of the lesion with sinus infiltration residual tumour in the vessel could not be removed. Both children were postoperatively treated with radiotherapy (craniospinal 36 Gy and boost to 54 Gy), concomitant Vincristin and adjuvant Cisplatin, Lomustine and Vincristine. RESULTS The gir...

Neuro-Oncology

INTRODUCTION Intracranial malignant germ cell tumours (iGCT) are rare brain tumours mainly diagno... more INTRODUCTION Intracranial malignant germ cell tumours (iGCT) are rare brain tumours mainly diagnosed in children and younger adults. MATERIAL AND METHODS A retrospective analysis was performed by chart review of patients treated for iGCT in the northern and central region of Denmark. Teratoma only patients were not included in the study. RESULTS 20 patients with iGCT were diagnosed from 2008–2019 in Western Denmark. The cumulative incidence was 1.05 per 100.000. The yearly incidence was 0.1 per 100.000. Mean age at diagnosis was 18 years (range 8–36 years), 17 were males and 3 were females. 13 patients presented with germinoma and 7 patients with non germinomateous germ cell tumours (NGGCT). Three patients had disseminated disease, two with germinoma and one with NGGCT. All patients had received radiotherapy and 18 patients were treated with multidrug chemotherapy including platinum and etoposide before irradiation. Two patients experienced recurrent disease, both non disseminated a...

Radiotherapy and Oncology