Petter Brandal

• Hannisdal, Marianne Hjellvik; Lundervold, Arvid; Goplen, Dorota Katarzyna Pazdyk; Brekke, Jorunn; Rahman, Mohummad Aminur & Brandal, Petter [Show all 10 contributors for this article] (2026). Spatial-temporal recurrence patterns of grade 4 glioma using deep learning integrated multiparametric MRI and molecular pathology. NPJ precision oncology. 10. doi: 10.1038/s41698-026-01557-0. Full text in Research Archive Show summary

  Grade 4 glioma is inherently lethal due to inevitable recurrence. Current radiotherapy guidelines recommend uniform target volume margins, disregarding molecular and clinical variables. We hypothesized that spatiotemporal recurrence may be predicted by molecular and phenotypic features present already at diagnosis. We analyzed 390 paired MRIs of grade 4 gliomas from Norwegian multi-centers and TCIA (2015–2025). Deep learning segmentation identified contrast-enhancing (CEcore) and non-enhancing (NE) tumor compartments and afflicted anatomical regions. We quantified primary CEcore/NE volume ratio, anatomical tumor trajectories, and spatiotemporal progression using Hausdorff-95—analyzed in relation to survival, MGMT, IDH, age, extent of resection, sex, and anatomical location, using machine learning and Cox regression. Primary tumor composition was independently prognostic: CEcore/NE volume ratio ≤0.324 predicted improved overall survival (adjusted HR = 0.56, 95% CI 0.37–0.84, p = 0.006), independent of age, MGMT-status, and individual compartments. Within IDH-wildtype, MGMT-unmethylated patients, low volume ratio ≤0.324 demonstrated a 4.3 months survival benefit (median 17.6 vs 13.3 months, p = 0.0209). Longer time to progression correlated with increased HD95 distances (p < 0.03). Tumors originating in occipital lobe had highest propensity to migrate to new sites (57.1%) and the shortest time to progression (adjusted HR = 1.90, p = 0.026). These findings support molecular-demographic-anatomical risk stratification that may inform personalized margin-determination in radiotherapy planning.

• Heggebø, Liv Cathrine; Fjæra, Lars Fredrik; Garrote, Frank Leonel Bello; Borgen, Ida Maria Henriksen; Blakstad, Hanne Kristin & Hellebust, Taran Annette Paulsen [Show all 14 contributors for this article] (2026). Case Report: Proton beam therapy – friend or foe for patients with IDH-mutated WHO grade 2 and 3 gliomas? Frontiers in Oncology. 16. doi: 10.3389/fonc.2026.1803943. Full text in Research Archive
• Heggebø, Liv Cathrine; Hellebust, Taran Annette Paulsen; Henry, Thomas; Fjæra, Lars Fredrik; Ottestad, Andreas & Rylander, Hillevi [Show all 36 contributors for this article] (2026). Radiotherapy quality assurance in the PRO-GLIO trial: results from a dummy run comparing experts across twelve institutions in two Scandinavian countries. Clinical and Translational Radiation Oncology. 60. doi: 10.1016/j.ctro.2026.101220. Full text in Research Archive
• Werlenius, Katja; Parcaoglu, Florida; Zupancic, Mark; Jakobsson, Frida; Flejmer, Anna & Kinhult, Sara [Show all 16 contributors for this article] (2026). Unexpected frequency of radiation induced contrast enhancement after proton radiotherapy in glioma patients treated within the Swedish PRO-CNS study. Radiotherapy and Oncology. ISSN 0167-8140. 221. doi: 10.1016/j.radonc.2026.111569. Full text in Research Archive
• Mireles, Eduardo Erasmo Mendoza; Blakstad, Hanne Kristin; Server, Andres Alonso; Leske, Henning; Skaga, Erlend & Aarhus, Mads [Show all 11 contributors for this article] (2026). Extent of resection and perioperative neurological status as prognostic markers in glioblastoma: a population-based study. Journal of Neuro-Oncology. ISSN 0167-594X. 177(1). doi: 10.1007/s11060-026-05481-y. Full text in Research Archive Show summary

  Purpose Maximal safe resection is the suggested standard for surgical treatment for patients with IDH-wildtype glioblastoma. Surgical safety is prioritized over radical extent of resection (EOR) because new neurological deficits are considered detrimental for survival. The aim of this study was to explore the combined impact of extent of resection and neurological status on survival in glioblastoma patients, using standardized tools for neurological function (neurological assessment in neuro-oncology (NANO scale) and extent of resection (RANO resect classification). Methods Population-based study of all adult patients who underwent resection for newly diagnosed glioblastoma from 2019 to 2022 in a geographically defined region. EOR was evaluated according to the RANO resect classification. Neurological function was assessed using the NANO scale preoperatively, immediately after surgery, and before start of radiotherapy. Kaplan Meier survival analysis, chi-square and log-rank tests were used to compare groups. Results The median overall survival (mOS) for 503 patients was 12.9 months. RANO resect class 1 was associated with significantly longer mOS compared to patients with RANO classes 2, 3, and 4 (21.0 vs. 14.8, 8.3, and 4.5 months, respectively; p < 0.01). Preoperatively neurologically intact patients (NANO-score 0) had a longer mOS, than patients with neurological deficits. Neither the postoperative NANO-score nor the change in the score impacted survival. Conclusions Being neurologically intact before surgery and supramaximal resection were independent, strong predictors of longer survival. Mild to moderate new postoperative neurological deficits did not impact mOS, suggesting that supramaximal resection may confer a survival benefit even when such deficits are induced.

• Heggebø, Liv Cathrine; Johannessen, Tor-Christian Aase; Magelssen, Henriette; Sprauten, Mette; Blakstad, Hanne Kristin & Brekke, Jorunn [Show all 11 contributors for this article] (2026). Norwegian consensus guidelines for selection of neuro-oncology patients to proton therapy. Clinical and Translational Radiation Oncology. 58. doi: 10.1016/j.ctro.2026.101140. Full text in Research Archive
• Furtner, Julia; Berchtold, Luzia; Rhun, Emilie Le; Silvani, Antonio; Rudà, Roberta & Lombardi, Giuseppe [Show all 17 contributors for this article] (2025). Prognostic value of 1D, 2D, and volumetric tumor size increases in recurrent WHO grade 2 and 3 meningiomas: Radiological post-hoc analysis of the EORTC-BTG-1320 trial. Neuro-Oncology Advances (NOA). 7(1). doi: 10.1093/noajnl/vdaf152. Full text in Research Archive
• Harba, Dima; Corell, Alba; Mansouri, Alireza; Brandal, Petter; Blomstrand, Malin & Jakola, Asgeir Store (2025). A scoping review of proton radiation therapy and mutant-isocitrate dehydrogenase-inhibitors in IDH mutated lower-grade gliomas: pushing beyond surrogate end-points. Acta Neurochirurgica. ISSN 0001-6268. 167(1). doi: 10.1007/s00701-025-06612-6. Full text in Research Archive Show summary

  Background Proton radiation therapy (PRT) and mutant isocitrate dehydrogenase inhibitors (mIDH-inhibitors) are emerging therapies for mIDH lower grade gliomas (LGGs). Despite their substantial theoretical benefits, comparisons with current standards – particularly pertaining to patient-centred outcomes – are limited. Methods Through PubMed and Scopus, a search strategy based on keywords focusing on PRT and mIDH-inhibitors was applied on December 3, 2024. Studies in English on at least 20 adult patients (≥ 18 years) with mIDH-LGG grade 2 or 3 and published between January 1, 2011 and August 31, 2024 were included. Review articles were excluded. Results Of 6383 identified articles, seven per treatment strategy were included. Overall survival was not reported for mIDH-inhibitors. The lack of high-quality studies comparing PRT to photon radiation therapy precludes conclusions regarding efficacy, effectiveness or even post-PRT radiological manifestations. For the mIDH-inhibitor Vorasidenib (AG-881), the radiological objective response rate was 10.0–42.9%, although lower for contrast-enhancing tumors. Vorasidenib significantly delayed tumor progression (27.7 versus 11.1 months, p < 0.001) and time to next intervention (not reached versus 17.8 months, p < 0.001) when compared to placebo. Adverse events were mostly mild, including elevated liver enzymes (15.6–44.2%) and headache (26.9–46.2%). Only 1/14 studies included assessments related to quality of life (QoL)-domains with inconclusive research on cognitive outcomes. Conclusion Studies reporting on patient-centred data including survival, cognition and QoL remain scarce. Larger, comparative prospective studies, preferably randomized controlled trials, with such outcomes are needed to inform clinicians whether the theoretical and radiological benefits can be translated to improved outcomes that matter to patients, i.e. living better and/or longer.

• Trewin-Nybråten, Cassia Bree; Lambert, Paul; Marienhagen, Kirsten; Andreassen, Lasse; Johannesen, Tom Børge & Niehusmann, Pitt [Show all 22 contributors for this article] (2025). Unveiling regional differences in glioblastoma patient survival with real-world data from the Norwegian brain tumor quality registry. Journal of Neuro-Oncology. ISSN 0167-594X. 175(3), p. 1355–1366. doi: 10.1007/s11060-025-05218-3. Full text in Research Archive
• Emblem, Kyrre E; Ringstad, Geir; Svensson, Siri Fløgstad; Vatnehol, Svein Are Sirirud; Storås, Tryggve Holck & Vik-Mo, Einar Osland [Show all 9 contributors for this article] (2025). Intrathecal contrast-enhanced MRI reveals an alternative route for drug delivery and brain tumor visualization. Cancer Letters. ISSN 0304-3835. 638. doi: 10.1016/j.canlet.2025.218152. Full text in Research Archive
• Mair, Maximilian J.; Lohmann, Philipp; Galldiks, Norbert; Belting, Mattias; Brandal, Petter & Broen, Martinus P.G. [Show all 25 contributors for this article] (2025). Availability and use of PET in patients with brain tumours – a European Organisation for Research and Treatment of Cancer - Brain Tumour Group (EORTC-BTG) survey. European Journal of Nuclear Medicine and Molecular Imaging. ISSN 1619-7070. 52(12), p. 4627–4638. doi: 10.1007/s00259-025-07366-0. Full text in Research Archive Show summary

  Purpose Positron emission tomography (PET) is increasingly used in neuro-oncology. However, little is known about its application across European institutions and reasons for variable implementation. Methods Between June and August 2024, members of the European Organisation for Research and Treatment of Cancer - Brain Tumour Group (EORTC-BTG) completed a cross-sectional online survey on PET use in neuro-oncological practice. Results Overall, 103 replies from 20 countries were received. A PET facility was available at 96/103 (93.2%) sites, of whom 74 (77.1%) performed PET in patients with brain tumours. Reasons for not performing PET included limited availability of tracers (14/29, 48.3%), high cost (11/29, 37.9%), and PET perceived unnecessary (8/29, 27.6%). Of sites performing PET, 69/74 (93.2%) reported use in glioma, 58/74 (78.4%) in brain metastasis, 52/74 (70.3%) in meningioma, and 46/74 (62.2%) in CNS lymphoma. Amino acid PET was performed at 62/71 centres (87.3%; 3 not reported [n.r.]), most frequently in glioma (58/59, 98.3%, 3 n.r.) and for differentiation of treatment-related changes from tumour progression (58/59, 98.3%). Somatostatin receptor (SSTR) PET was performed at 50/68 sites (73.5%, 6 n.r.), mainly in meningioma (48/49, 98.0%), for patient selection before radioligand therapy (41/49, 83.7%) and for radiotherapy target volume definition (33/49, 67.3%). Unrestricted coverage by statutory health insurance was reported by 46/59 (78.0%) centres for amino acid PET and 33/49 (67.3%) for SSTR PET. Conclusion PET use in neuro-oncology is variable across EORTC-BTG sites. Generation of evidence in clinical trials and surveys including non-academic institutions are needed to guide implementation in clinical practice.

• Heggebø, Liv Cathrine; Garrote, Frank Leonel Bello; Fjæra, Lars Fredrik; Hervani, Maziar; Ramberg, Christina & Ottestad, Andreas [Show all 14 contributors for this article] (2025). Protons or Photons in Pituitary Neuroendocrine Tumors—That Is Not the Question. International Journal of Particle Therapy (IJPT). 17. doi: 10.1016/j.ijpt.2025.101194. Full text in Research Archive Show summary

  Purpose With the long-life expectancy of patients with pituitary neuroendocrine tumors (PitNETs), reducing long-term toxicity is essential to preserve quality of life. We aimed to investigate whether 2- or 3-field proton beam therapy (PBT) plans better spare organs at risks (OARs), including healthy tissue, than volumetric modulated arc photon therapy (VMAT). Materials and Methods Fifteen consecutive patients who had received radiation therapy for PitNETs were included. We made 4 treatment plans for each patient: one 3-field PBT plan (3F), two 2-field PBT plans (2F-L and 2F-IV), and 1 VMAT plan. Dosing was set to 1.8 Gy × 30 to allow for dosimetric comparisons. Results All 4 treatment techniques showed excellent target volume coverage. Compared to VMAT, the 3 PBT techniques had lower doses to OARs. Median D40% to the hippocampi varied from 0.4 to 1.1 Gy (relative biological effectiveness [RBE]) with PBT and was 5.2 Gy for both hippocampi for VMAT. Median mean dose to brain-CTV and head-CTV were lowest for 2F-L (3.1 and 2.3 Gy [RBE]), followed by 3F (3.9 and 2.5 Gy [RBE]), 2F-IV (4.1 and 2.6 Gy [RBE]), and highest for VMAT (4.8 and 4.7 Gy). A relative reduction in integral dose compared to VMAT was seen for all PBT techniques, with a median reduction of 38.5% to 45.9% for head-CTV. Conclusion Proton techniques spared OARs better than VMAT; however, absolute dose sparing was relatively small, and the clinical value remains uncertain. Nonetheless, the dose reduction, especially for the hippocampi and integral dose, is probably clinically meaningful. We argue that head-CTV should be assessed, as much of the volume receiving dose is located outside the brain. The size and location of the target volume impacted which proton plan was preferable. We conclude that individualized planning is more important than a mere question on protons or photons in PitNET patients.

• Liu, Qinghui; Fuster-Garcia, Elies; Hovden, Ivar Thokle; MacIntosh, Bradley; Grødem, Edvard Olaf Sætersdal & Brandal, Petter [Show all 12 contributors for this article] (2025). Treatment-aware Diffusion Probabilistic Model for Longitudinal MRI Generation and Diffuse Glioma Growth Prediction. IEEE Transactions on Medical Imaging. ISSN 0278-0062. 44(6). doi: 10.1109/TMI.2025.3533038. Full text in Research Archive
• Tabouret, Emeline; Furtner, Julia; Graillon, Thomas; Silvani, Antonio; Rhun, Emilie Le & Soffietti, Riccardo [Show all 16 contributors for this article] (2024). 3D volume growth rate evaluation in the EORTC-BTG-1320 clinical trial for recurrent WHO grade 2 and 3 meningiomas. Neuro-Oncology. ISSN 1522-8517. 26(7), p. 1302–1309. doi: 10.1093/neuonc/noae037. Full text in Research Archive
• Skaga, Erlend; Trewin-Nybråten, Cassia Bree; Niehusmann, Pitt; Johannessen, Tom Børge; Marienhagen, Kirsten & Oltedal, Leif [Show all 14 contributors for this article] (2024). Stable glioma incidence and increased patient survival over the past two decades in Norway: a nationwide registry-based cohort study. Acta Oncologica. ISSN 0284-186X. 63(1), p. 83–94. doi: 10.2340/1651-226X.2024.24970. Full text in Research Archive Show summary

  Background: Surveillance of incidence and survival of central nervous system tumors is essential to monitor disease burden and epidemiological changes, and to allocate health care resources. Here, we describe glioma incidence and survival trends by histopathology group, age, and sex in the Norwegian population. Material and methods: We included patients with a histologically verified glioma reported to the Cancer Registry of Norway from 2002 to 2021 (N = 7,048). Population size and expected mortality were obtained from Statistics Norway. Cases were followed from diagnosis until death, emigration, or 31 December 2022, whichever came first. We calculated age-standardized incidence rates (ASIR) per 100,000 person-years and age-standardized relative survival (RS). Results: The ASIR for histologically verified gliomas was 7.4 (95% CI: 7.3–7.6) and was higher for males (8.8; 95% CI: 8.5–9.1) than females (6.1; 95% CI: 5.9–6.4). Overall incidence was stable over time. Glioblastoma was the most frequent tumor entity (ASIR = 4.2; 95% CI: 4.1–4.4). Overall, glioma patients had a 1-year RS of 63.6% (95% CI: 62.5–64.8%), and a 5-year RS of 32.8% (95% CI: 31.6–33.9%). Females had slightly better survival than males. For most entities, 1- and 5-year RS improved over time (5-year RS for all gliomas 29.0% (2006) and 33.1% (2021), p < 0.001). Across all tumor types, the RS declined with increasing age at diagnosis. Interpretation: The incidence of gliomas has been stable while patient survival has increased over the past 20 years in Norway. As gliomas represent a heterogeneous group of primary CNS tumors, regular reporting from cancer registries at the histopathology group level is important to monitor disease burden and allocate health care resources in a population.

• Prysiazhniuk, Yeva; Server, Andrés; Leske, Henning; Gadmar, Øystein Bech; Helseth, Eirik & Eijgelaar, Roelant Sjouke [Show all 12 contributors for this article] (2024). Diffuse glioma molecular profiling with arterial spin labeling and dynamic susceptibility contrast perfusion MRI: A comparative study. Neuro-Oncology Advances (NOA). 6(1). doi: 10.1093/noajnl/vdae113. Full text in Research Archive Show summary

  Background Evaluation of molecular markers (IDH, pTERT, 1p/19q codeletion, and MGMT) in adult diffuse gliomas is crucial for accurate diagnosis and optimal treatment planning. Dynamic Susceptibility Contrast (DSC) and Arterial Spin Labeling (ASL) perfusion MRI techniques have both shown good performance in classifying molecular markers, however, their performance has not been compared side-by-side. Methods Pretreatment MRI data from 90 patients diagnosed with diffuse glioma (54 men/36 female, 53.1 ± 15.5 years, grades 2–4) were retrospectively analyzed. DSC-derived normalized cerebral blood flow/volume (nCBF/nCBV) and ASL-derived nCBF in tumor and perifocal edema were analyzed in patients with available IDH-mutation (n = 67), pTERT-mutation (n = 39), 1p/19q codeletion (n = 33), and MGMT promoter methylation (n = 31) status. Cross-validated uni- and multivariate logistic regression models assessed perfusion parameters’ performance in molecular marker detection. Results ASL and DSC perfusion parameters in tumor and edema distinguished IDH-wildtype (wt) and pTERT-wt tumors from mutated ones. Univariate classification performance was comparable for ASL-nCBF and DSC-nCBV in IDH (maximum AUROCC 0.82 and 0.83, respectively) and pTERT (maximum AUROCC 0.70 and 0.81, respectively) status differentiation. The multivariate approach improved IDH (DSC-nCBV AUROCC 0.89) and pTERT (ASL-nCBF AUROCC 0.8 and DSC-nCBV AUROCC 0.86) classification. However, ASL and DSC parameters could not differentiate 1p/19q codeletion or MGMT promoter methylation status. Positive correlations were found between ASL-nCBF and DSC-nCBV/-nCBF in tumor and edema. Conclusions ASL is a viable gadolinium-free replacement for DSC for molecular characterization of adult diffuse gliomas.

• Heggebø, Liv Cathrine; Blakstad, Hanne Kristin; Eriksson, Marlena Christina & Brandal, Petter (2024). Lomustine overdose in a patient with diffuse glioma: Symptoms, management and outcome. BMJ Case Reports. 17(7). doi: 10.1136/bcr-2024-260450. Full text in Research Archive
• Halldórsso, Skarphéðinn; Nagymihaly, Richard; Patel, Areeba; Brandal, Petter; Panagopoulos, Ioannis & Leske, Henning [Show all 9 contributors for this article] (2024). Accurate and comprehensive evaluation of O6-methylguanine-DNA methyltransferase promoter methylation by nanopore sequencing. Neuropathology and Applied Neurobiology. ISSN 0305-1846. 50(3). doi: 10.1111/nan.12984. Full text in Research Archive Show summary

  Aims The methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter region is essential in evaluating the prognosis and predicting the drug response in patients with glioblastoma. In this study, we evaluated the utility of using nanopore long-read sequencing as a method for assessing methylation levels throughout the MGMT CpG-island, compared its performance to established techniques and demonstrated its clinical applicability. Methods We analysed 165 samples from CNS tumours, focusing on the MGMT CpG-island using nanopore sequencing. Oxford Nanopore Technologies (ONT) MinION and PromethION flow cells were employed for single sample or barcoded assays, guided by a CRISPR/Cas9 protocol, adaptive sampling or as part of a whole genome sequencing assay. Methylation data obtained through nanopore sequencing were compared to results obtained via pyrosequencing and methylation bead arrays. Hierarchical clustering was applied to nanopore sequencing data for patient stratification. Results Nanopore sequencing displayed a strong correlation (R2 = 0.91) with pyrosequencing results for the four CpGs of MGMT analysed by both methods. The MGMT-STP27 algorithm's classification was effectively reproduced using nanopore data. Unsupervised hierarchical clustering revealed distinct patterns in methylated and unmethylated samples, providing comparable survival prediction capabilities. Nanopore sequencing yielded high-confidence results in a rapid timeframe, typically within hours of sequencing, and extended the analysis to all 98 CpGs of the MGMT CpG-island. Conclusions This study presents nanopore sequencing as a valid and efficient method for determining MGMT promotor methylation status. It offers a comprehensive view of the MGMT promoter methylation landscape, which enables the identification of potentially clinically relevant subgroups of patients. Further exploration of the clinical implications of patient stratification using nanopore sequencing of MGMT is warranted.

• Blakstad, Hanne Kristin; Mireles, Eduardo Erasmo Mendoza; Kierulf-Vieira, Kirsten Strømme; Singireddy, Divija; Mdala, Ibrahimu & Heggebø, Liv Cathrine [Show all 16 contributors for this article] (2024). The impact of cancer patient pathway on timing of radiotherapy and survival: a cohort study in glioblastoma patients. Journal of Neuro-Oncology. ISSN 0167-594X. 169, p. 137–145. doi: 10.1007/s11060-024-04709-z. Full text in Research Archive Show summary

  Purpose Glioblastoma (GBM) is an aggressive brain tumor in which primary therapy is standardized and consists of surgery, radiotherapy (RT), and chemotherapy. However, the optimal time from surgery to start of RT is unknown. A high-grade glioma cancer patient pathway (CPP) was implemented in Norway in 2015 to avoid non-medical delays and regional disparity, and to optimize information flow to patients. This study investigated how CPP affected time to RT after surgery and overall survival. Methods This study included consecutive GBM patients diagnosed in South-Eastern Norway Regional Health Authority from 2006 to 2019 and treated with RT. The pre CPP implementation group constituted patients diagnosed 2006–2014, and the post CPP implementation group constituted patients diagnosed 2016–2019. We evaluated timing of RT and survival in relation to CPP implementation. Results A total of 1212 patients with GBM were included. CPP implementation was associated with significantly better outcomes (p < 0.001). Median overall survival was 12.9 months. The odds of receiving RT within four weeks after surgery were significantly higher post CPP implementation (p < 0.001). We found no difference in survival dependent on timing of RT below 4, 4–6 or more than 6 weeks (p = 0.349). Prognostic factors for better outcomes in adjusted analyses were female sex (p = 0.005), younger age (p < 0.001), solitary tumors (p = 0.008), gross total resection (p < 0.001), and higher RT dose (p < 0.001). Conclusion CPP implementation significantly reduced time to start of postoperative RT. Survival was significantly longer in the period after the CPP implementation, however, timing of postoperative RT relative to time of surgery did not impact survival.

• Tauziède-Espariat, Arnault; Nicaise, Yvan; Sievers, Philipp; Sahm, Felix; Deimling, Andreas von & Guillemot, Delphine [Show all 45 contributors for this article] (2024). CNS tumors with PLAGL1-fusion: beyond ZFTA and YAP1 in the genetic spectrum of supratentorial ependymomas. Acta neuropathologica communications. 12(1). doi: 10.1186/s40478-023-01695-7. Full text in Research Archive
• Blakstad, Hanne Kristin; Brekke, Jorunn; Rahman, Mohummad Aminur; Arnesen, Victoria Smith; Miletic, Hrvoje & Brandal, Petter [Show all 9 contributors for this article] (2023). Survival in a consecutive series of 467 glioblastoma patients: Association with prognostic factors and treatment at recurrence at two independent institutions. PLOS ONE. 18(2). doi: 10.1371/journal.pone.0281166. Full text in Research Archive Show summary

  Therapy of recurrent glioblastoma (GBM) is challenging due to lack of standard treatment. We investigated physicians’ treatment choice at recurrence and prognostic and predictive factors for survival in GBM patients from Norway’s two largest regional hospitals. Clinicopathological data from n = 467 patients treated at Haukeland and Oslo university hospitals from January 2015 to December 2017 was collected. Data included tumour location, promoter methylation of O6 methylguanine-DNA methyltransferase (MGMT) and mutation of isocitrate dehydrogenase (IDH), patient age, sex, extent of resection at primary diagnosis and treatment at successive tumour recurrences. Cox-proportional hazards regression adjusting for multiple risk factors was used. Median overall survival (OS) was 12.1 months and 21.4% and 6.8% of patients were alive at 2 and 5 years, respectively. Median progression-free survival was 8.1 months. Treatment at recurrence varied but was not associated with difference in overall survival (OS) (p = 0.201). Age, MGMT hypermethylation, tumour location and extent of resection were independent prognostic factors. Patients who received 60 Gray radiotherapy with concomitant and adjuvant temozolomide at primary diagnosis had 16.1 months median OS and 9.3% were alive at 5 years. Patients eligible for gamma knife/stereotactic radiosurgery alone or combined with chemotherapy at first recurrence had superior survival compared to chemotherapy alone (p<0.001). At second recurrence, combination chemotherapy with or without bevacizumab were both superior to no treatment. Treatment at recurrence differed between the institutions but there was no difference in median OS, indicating that it is the disease biology that dictates patient outcome.

• Blakstad, Hanne Kristin; Mireles, Eduardo Erasmo Mendoza; Heggebø, Liv Cathrine; Magelssen, Henriette; Sprauten, Mette & Johannesen, Tom Børge [Show all 13 contributors for this article] (2023). Incidence and outcome of pseudoprogression after radiation therapy in glioblastoma patients: A cohort study. Neuro-Oncology Practice. ISSN 2054-2577. 11(1), p. 36–45. doi: 10.1093/nop/npad063. Full text in Research Archive
• Mireles, Eduardo Erasmo Mendoza; Skaga, Erlend; Server, Andrés; Leske, Henning; Brandal, Petter & Helseth, Eirik [Show all 8 contributors for this article] (2023). The benefit of complete resection of contrast enhancing tumor in glioblastoma patients: A population-based study. Neuro-Oncology Practice. ISSN 2054-2577. 10(6), p. 555–564. doi: 10.1093/nop/npad037. Full text in Research Archive Show summary

  Abstract Background New treatment modalities have not been widely adopted for patients with glioblastoma (GBM) after the addition of temozolomide to radiotherapy. We hypothesize that increased extent of resection (EOR) has resulted in improved survival for surgically treated patients with glioblastoma at the population level. Methods Retrospective analysis of adult patients operated for glioblastoma in the population of South–Eastern Norway. Patients were stratified into Pre-temozolomide- (2003–2005), temozolomide- (2006–2012), and resection-focused period (2013–2019) and evaluated according to age and EOR. Results The study included 1657 adult patients operated on for supratentorial glioblastoma. The incidence of histologically confirmed glioblastoma increased from 3.7 in 2003 to 5.3 per 100 000 in 2019. The median survival was 11.4 months. Complete resection of contrast-enhancing tumor (CRCET) was achieved in 386 patients, and this fraction increased from 13% to 32% across the periods. Significant improvement in median survival was found between the first 2 periods and the last (10.5 and 10.6 vs. 12.3 months; P &amp;lt; .01), with a significant increase in 3- and 5-year survival probability to 12% and 6% (P &amp;lt; .01). Patients with CRCET survived longer than patients with non-CRCET (16.1 vs. 10.8 months; P &amp;lt; .001). The median survival doubled in patients ≥70 years and (12.1 months). Survival was similar between the time periods in patients where CRCET was achieved. Conclusions We demonstrate an improved survival of GBM patients at the population level associated with an increased fraction of patients with CRCET. The data support the importance of CRCET to improve glioblastoma patient outcomes.

• Preusser, Matthias; Silvani, Antonio; Rhun, Emilie Le; Soffietti, Riccardo; Lombardi, Giuseppe & Sepulveda, Juan Manuel [Show all 38 contributors for this article] (2022). Trabectedin for recurrent WHO grade 2 or 3 meningioma: A randomized phase II study of the EORTC Brain Tumor Group (EORTC-1320-BTG). Neuro-Oncology. ISSN 1522-8517. 24(5), p. 755–767. doi: 10.1093/neuonc/noab243. Full text in Research Archive
• Tanem, Kristine Eidal; Stensvold, Einar; Wilberg, Petter; Skaare, Anne B; Brandal, Petter & Herlofson, Bente Brokstad (2022). Oral and dental late effects in long-term survivors of childhood embryonal brain tumors. Supportive Care in Cancer. ISSN 0941-4355. 30, p. 10233–10241. doi: 10.1007/s00520-022-07405-8. Full text in Research Archive Show summary

  Abstract Purpose To investigate oral and dental late effects in survivors of childhood brain tumors medulloblastoma (MB) and central nervous system supratentorial primitive neuroectodermal tumor (CNS-PNET). Methods This cross-sectional study assessed oral and dental late effects in MB/CNS-PNET survivors treated before 20 years of age, and with a minimum of 2 years since treatment. Participants went through an oral and radiographic examination. We assessed oral status using the decayed-missing-filled index (DMFT), oral dryness, maximum mouth opening (MMO), fungal infection, and registration of dental developmental disturbances (DDD) in the form of hypodontia, microdontia, and enamel hypoplasia. Results The 46 participants’ mean age at enrolment was 27 ± 12.8 years and at treatment 8.5 ± 5.2 years, and the mean time since treatment was 18.9 ± 12 years. Over a third (35%) of survivors had reduced mouth opening (mean 29.3 ± 5.6 mm (range 16–35)). A significantly lower MMO was found in individuals treated ≤ 5 years compared to survivors treated &gt; 5 years ( p  = 0.021). One or more DDD were registered in 30.4% of the survivors, with a significantly higher prevalence in individuals treated ≤ 5 years ( p  &lt; 0.001). Hypodontia was the most prevalent type of DDD. There was no difference in DMFT score in relation to age at treatment. Oral dryness was not frequently reported or observed in these survivors. Conclusion Survivors of childhood MB/CNS-PNET are at risk of oral and dental late effects including reduced mouth opening and DDD. The risk is highest in survivors treated before the age of 5.

• Tanem, Kristine Eidal; Stensvold, Einar; Wilberg, Petter; Skaare, Anne B; Singh, Preet Bano & Brandal, Petter [Show all 7 contributors for this article] (2022). Taste and smell function in long-term survivors after childhood medulloblastoma/CNS-PNET. Supportive Care in Cancer. ISSN 0941-4355. 30, p. 6155–6162. doi: 10.1007/s00520-022-07048-9. Full text in Research Archive Show summary

  Abstract Purpose To investigate taste and smell function in survivors, with a minimum of 2 years since treatment of childhood medulloblastoma (MB)/central nervous system supratentorial primitive neuroectodermal tumor (CNS-PNET). Methods This cross-sectional study included 40 survivors treated ≤ 20 years of age. Taste strips with four concentrations of sweet, sour, salt, and bitter were used to assess taste function in all participants. Score from 0 to 16; ≥ 9 normogeusia, &lt; 9 hypogeusia, and complete ageusia which equals no sensation. No sensation of a specific taste quality equals ageusia of that quality. Thirty-two participants conducted smell testing using three subtests of Sniffin’ sticks: threshold, discrimination, and identification. Together they yield a TDI-score from 1 to 48; functional anosmia ≤ 16.00, hyposmia &gt; 16.00– &lt; 30.75, normosmia ≥ 30.75– &lt; 41.50, and ≥ 41.50 hyperosmia. Results were compared with normative data. Survivors rated their taste and smell function using a numerical rating scale (NRS) score 0–10. Results Forty survivors with a mean time since treatment of 20.5 years, 13 (32.5%) were diagnosed with hypogeusia, nine (22.5%) of these being ageusic to one or more taste qualities. Seventeen (53%) of 32 participants were diagnosed with hyposmia. The mean scores of the olfactory subtests, and TDI score were significantly lower than normative data ( P  &lt; 0.0001). The mean NRS scores of smell and taste function were 7.9 ± 1.5 and 8 ± 1.3, respectively. Conclusion Our study showed impaired taste and smell function in survivors of childhood MB/CNS-PNET using objective measurements. However, subjective ratings did not reflect objective findings.

• Niehusmann, Pitt; Stensvold, Einar; Leske, Henning; Pietsch, Torsten; Goschzik, Tobias & Gielen, Gerrit H. [Show all 10 contributors for this article] (2022). Molecular pathological insights reveal a high number of unfavorable risk patients among children treated for medulloblastoma and CNS-PNET in Oslo 2005–2017. Pediatric Blood & Cancer. ISSN 1545-5009. 69(9), p. 1–8. doi: 10.1002/pbc.29736. Full text in Research Archive Show summary

  Background An unexplained regional difference in survival was observed in previous publications on outcome for children treated for medulloblastoma and supratentorial primitive neuroectodermal tumor (CNS-PNET) in Norway. We aimed now to reevaluate and perform a retrospective molecular-based risk stratification of all embryonal brain tumors (excluding atypical teratoid rhabdoid tumors [ATRT]) in pediatric patients, who underwent surgery and treatment at Oslo University Hospital between 2005 and 2017. Procedure Specimens from all patients <20 years of age with initial diagnosis of medulloblastoma or CNS-PNET were reviewed. Molecular analyses comprised NanoString gene expression, molecular inversion probe profiling, Sanger sequencing, and 850K-methylation analysis. Whole chromosomal aberration signatures were assessed in standard-risk non-WNT/non-SHH medullobastomas for molecular risk stratification. Results We identified 53 non-ATRT embryonal tumors among which 33 were medulloblastomas. Molecular genetic parameters including whole chromosomal aberration signatures allowed classification of 17 medulloblastomas as molecular high risk. These patients had a significantly worse 5-year overall survival than the remaining 16 medulloblastoma patients (52.9% vs. 87.1% p = 0.036). Five patients in our cohort had tumors that are considered as new entities in the 2021 classification of tumors of the central nervous system. Five tumors were re-classified as nonembryonal tumors after review. Conclusion Molecular-based risk stratification of standard-risk non-WNT/non-SHH medulloblastoma enabled superior identification of medulloblastomas with dismal prognosis. Our cohort demonstrated a significantly increased fraction of standard-risk non-WNT/non-SHH medulloblastoma with molecular high-risk profile compared to other studies, which might have contributed to previously reported unfavorable outcome data.

• Kvammen, Janne Anita; Stensvold, Einar; Godang, Kristin; Bollerslev, Jens; Myklebust, Tor Åge & Brandal, Petter [Show all 8 contributors for this article] (2022). Bone mineral density and nutrition in long-term survivors of childhood brain tumors. Clinical Nutrition ESPEN. ISSN 2405-4577. 50, p. 162–169. doi: 10.1016/j.clnesp.2022.05.025. Full text in Research Archive Show summary

  Background and aims Childhood cancer survivors are at risk of unwanted late effects. The primary aim of this study was to assess bone mineral density Z-scores (BMDz) in long-term survivors of childhood medulloblastoma (MB) or central nervous system supratentorial primitive neuroectodermal tumor (CNS-PNET). Secondary aims were to describe nutrient intake, vitamin D status, physical activity and explore potential risk factors for decreased BMDz. Methods All MB and CNS-PNET survivors treated at Oslo University Hospital from 1974 to 2013 were invited to participate in a cross-sectional study. Dual-energy x-ray absorptiometry (Lunar Prodigy) assessed BMDz lumbar spine, BMDz total body, and lean body mass. Decreased BMDz was defined as a combination of low BMDz −1 to −1.99 and very low BMDz ≤−2. Lean body mass index (LMI) was calculated by dividing lean body mass by the squared height. Nutrient intake was assessed by a 3-day food record. Serum 25(OH)D was analyzed. Physical activity was reported by a questionnaire. Descriptive statistics and multivariable Cox regression analyses were applied. Results Fifty survivors with a median age of 25.5 years (5.5–51.9) and a median follow-up time of 19.5 years (3.2–40.5) were included. Mean BMDz lumbar spine was −0.8 (SD 1.1, 95% CI: −1.1 to −0.4), and BMDz total body was −0.6 (SD 1.1, 95% CI: −0.9 to −0.3). Decreased BMDz was detected in 48% of the lumbar spine and 34% of the total body measurements. In all, 62% had low calcium, and 69% had low vitamin D intake. 26% of participants had serum 25(OH)D < 50 nmol/L, and 62% reported an inactive lifestyle. Male sex, higher age at diagnosis, and lower LMI were potential risk factors for decreased BMDz. Conclusions Long-term survivors of childhood MB and CNS-PNET had decreased BMDz, and risk factors were male sex, higher age at diagnosis, and lower LMI. Inadequate calcium and vitamin D intake, an inactive lifestyle, and a high prevalence of 25(OH)D ≤ 50 nmol/L were detected.

• Lundar, Tryggve; Due-Tønnessen, Bernt Johan; Frič, Radek; Sundseth, Jarle Østberg; Brandal, Petter & Due-Tønnessen, Paulina (2021). Outcome After Treatment of Spinal Ependymoma in Children and Adolescents: Long-Term Follow-up of a Single Consecutive Institutional Series of 33 Patients Treated Over Eight Decades. World Neurosurgery. ISSN 1878-8750. 150, p. E228–E235. doi: 10.1016/j.wneu.2021.02.131. Full text in Research Archive Show summary

  Background Long-term outcomes for pediatric patients treated for spinal ependymoma are unknown. Methods We performed a retrospective analysis of outcome data from 33 children and young adults (0–22 years) who were operated on for a spinal ependymoma at our institution during the last 8 decades (1938–2019). Results Nineteen patients are alive, with follow-up period up to 60 years. Twelve of them are tumor-free, and 7 are alive with disease. Fourteen patients are dead, 9 of them due to recurrent and/or progressive disease 1–56 years (median: 11 years) after the initial surgery. Four of the deceased patients were treated before 1948, 3 of them with excellent long-term survival for 62–66 years after the initial surgery. Tumor recurrence was observed in half of the patients, both local at the site of the primary tumor resection as well as widespread intraspinal presentations. Recurrences were observed within months but also occurred after up to 20 years after initial treatment. After the implementation of magnetic resonance imaging in 1987, details of recurrent disease became more easily demonstrated. Repeated resections were performed when the symptomatic spinal disease was in progress (n = 11). Furthermore, 2 patients have intracranial tumor manifestations, 1 of them underwent resection of a suprasellar tumor in 1991. Four deceased patients experienced aggressive extraspinal progressive disease requiring multiple surgeries, including pulmonary metastasis in 1 of them. Conclusions Pediatric spinal ependymomas can be treated with favorable results and functional outcome may be good even after more than half a century of follow-up. Nevertheless, unexpected and late recurrences may occur, and life-long follow-up is therefore recommended.

• Husum, Yngvil Solheim; Skogen, Karoline; Brandal, Petter; Rønning, Pål Andre; Wigers, Andreas Reidar & Evang, Johan Arild [Show all 7 contributors for this article] (2021). Bilateral calcification of the optic nerve sheath: A diagnostic dilemma. American Journal of Ophthalmology Case Reports. 22, p. 1–4. doi: 10.1016/j.ajoc.2021.101106. Full text in Research Archive
• Switlyk, Marta Daniela; Niehusmann, Pitt; Sprauten, Mette; Magelssen, Henriette; Aarhus, Mads & Rasmussen, Finn [Show all 8 contributors for this article] (2021). Neurosarcoidosis resembling multiple meningiomas: A misleading presentation of the disease and diagnostic challenge. Acta Radiologica Open. 10(7), p. 1–8. doi: 10.1177/20584601211036550. Full text in Research Archive Show summary

  Sarcoidosis is characterized by the presence of noncaseating granulomatous inflammation in the affected organs. Neurosarcoidosis denotes the involvement of the nervous system and can be either isolated or coexisting with extraneural systemic inflammation. The diagnosis of isolated neurosarcoidosis may be challenging due to unspecific symptoms and similar appearances with other disease processes. This report presents an uncommon case of intracranial sarcoidosis mimicking multiple meningiomas. Familiarity with the spectrum of magnetic resonance imaging findings in neurosarcoidosis is crucial to prevent interpretive errors which may in turn lead to an inappropriate diagnosis and treatment.

• Lundar, Tryggve; Due-Tønnessen, Bernt Johan; Frič, Radek; Brandal, Petter & Due-Tønnessen, Paulina (2021). Choroid plexus tumors in children: Long-term follow-up of consecutive single-institutional series of 59 patients treated over a period of 8 decades (1939-2020). World Neurosurgery. ISSN 1878-8750. 158, p. e810–e819. doi: 10.1016/j.wneu.2021.11.070. Full text in Research Archive Show summary

  Objective To present long-term follow-up of a consecutive single-institutional series of patients treated for choroid plexus tumors over 8 decades. Methods From 1939 to 2020, 59 children were treated for choroid plexus tumors. Median age at diagnosis was 1.7 years. Results Gross total resection was achieved in 51 patients (86%). Ten patients (17%) underwent >1 resection. During the first 4 decades of the study (1939–1979), 14 patients with plexus papillomas were treated. Operative mortality was 50%, with 6 of the remaining 7 patients experiencing excellent survival with follow-up periods of 41–81 years. In the last 4 decades (1980–2020), 38 patients had low-grade tumors, and all were alive at the latest follow-up (range, 0.5–39 years). Observed 5-year survival in this subgroup was 100% (n = 30), as was observed 10-year survival (n = 26). One of 7 (14%) patients with atypical choroid plexus papilloma and 3 of 31 patients (10%) with choroid plexus papilloma underwent a second resection owing to recurrent tumor. At last follow-up, 47 patients (80%) were alive; 45 (96%) had a Barthel Index score of 100 and 2 had a Barthel Index score of 50. Today 25 patients are adults (20–59 years old); 17 work full-time, 4 work part-time, and 4 are unable to work. Conclusions Low-grade choroid plexus tumors can be cured with gross total resection alone, with excellent long-term survival and functionality. The vast majority of survivors live independently as adults and work full-time. Recurrences are uncommon (8.7%), appear within the first few years after primary surgery, and can be treated with repeat resections.

• Skaga, Erlend; Skretteberg, Marthe Andrea; Johannesen, Tom Børge; Brandal, Petter; Vik-Mo, Einar O. & Helseth, Eirik [Show all 7 contributors for this article] (2021). Real-world validity of randomized controlled phase III trials in newly diagnosed glioblastoma: To whom do the results of the trials apply? Neuro-Oncology Advances (NOA). 3(1). doi: 10.1093/noajnl/vdab008. Full text in Research Archive Show summary

  Background The survival rates in population-based series of glioblastoma (GBM) differ substantially from those reported in clinical trials. This discrepancy may be attributed to that patients recruited to trials tend to be younger with better performance status. However, the proportion and characteristics of the patients in a population considered either eligible or ineligible for trials is unknown. The generalizability of trial results is therefore also uncertain. Methods Using the Cancer Registry of Norway and the Brain Tumor Database at Oslo University Hospital, we tracked all patients within a well-defined geographical area with newly diagnosed GBM during the years 2012–2017. Based on data from these registries and the medical records, the patients were evaluated for trial eligibility according to criteria employed in recent phase III trials for GBM. Results We identified 512 patients. The median survival was 11.7 months. When we selected a potential trial population at the start of concurrent chemoradiotherapy (radiotherapy [RT]/ temozolomide [TMZ]) by the parameters age (18–70 y), passed surgery for a supratentorial GBM, Eastern Cooperative Oncology Group (ECOG) ≤2, normal hematologic, hepatic and renal function, and lack of severe comorbidity, 57% of the patients were excluded. Further filtering the patients who progressed during RT/TMZ and never completed RT/TMZ resulted in exclusion of 59% and 63% of the patients, respectively. The survival of patients potentially eligible for trials was significantly higher than of the patients not fulfilling trial eligibility criteria (P < .0001). Conclusions Patients considered eligible for phase III clinical trials represent a highly selected minority of patients in a real-world GBM population.

• Lundar, Tryggve; Due-Tønnessen, Bernt Johan; Frič, Radek; Sundseth, Jarle Østberg; Brandal, Petter & Due-Tønnessen, Paulina (2021). Outcome after treatment of pediatric supratentorial ependymoma: long-term follow-up of a single consecutive institutional series of 26 patients. British Journal of Neurosurgery. ISSN 0268-8697. p. 1–9. doi: 10.1080/02688697.2021.1914821. Full text in Research Archive Show summary

  Background Long-term outcome after surgical treatment of supratentorial ependymoma (STE) in children has not been extensively reported. Findings We identified 26 children who underwent primary tumor resection of STE between 1953 and 2011, with at least 8 years follow-up. Ten patients (38%) had anaplastic and 16 had low grade ependymoma. Four of 15 children (26%) treated in the years 1953–1976 survived more than 5 years, but the observed 10-year survival was only 7%. One patient lived for 37 years, and second surgery for a local recurrent lesion disclosed a glioblastoma, possibly secondary to radiotherapy. In contrast, the observed 5-year survival rate for 11 children treated in the years 1992–2011 was 8/11 (73%) and observed 10- and 25-year survival rates were 70% and 66%, respectively. Eight patients were alive and tumor-free with follow-up periods of 8–27 (median 18) years, all treated after 1992. Five of these long-term survivors were 23–39 years old with full-time (n = 3) or part-time (n = 2) work. The last three patients were still children (9–12 years old): one with good function and two with major neurological deficits. The majority of patients (n = 18) received adjuvant radiotherapy and eight children no adjuvant treatment. Repeated resections for residual or recurrent tumor were necessary in 11 patients (42%), mostly due to local disease with progressive clinical symptoms. Eight patients underwent only one repeat resection, whereas three patients had two or more repeat resections within 18 years after initial surgery. Four patients were tumor-free after repeated resections at the latest follow-up, 2–13 years after last surgery. Conclusion Pediatric STE has a marked risk for local recurrence even after gross total resection and postoperative radiotherapy, but survival has increased following the introduction of modern treatment in recent years. Repeated surgery is an important part of treatment and may lead to persistent tumor control.

• Brandal, Petter; Bergfeldt, Kjell; Aggerholm-Pedersen, Ninna; Bäckström, Gloria; Kerna, Irina & Gubanski, Michael [Show all 16 contributors for this article] (2020). A Nordic-Baltic perspective on indications for proton therapy with strategies for identification of proper patients. Acta Oncologica. ISSN 0284-186X. 59(10), p. 1157–1163. doi: 10.1080/0284186X.2020.1817977. Full text in Research Archive
• Clarke, Matthew; Mackay, Alan; Ismer, Britta; Pickles, Jessica C.; Tatevossian, Ruth G. & Newman, Scott [Show all 51 contributors for this article] (2020). Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes. Cancer Discovery. ISSN 2159-8274. 10(7), p. 942–963. doi: 10.1158/2159-8290.CD-19-1030. Full text in Research Archive Show summary

  Infant high-grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases under 4 years of age, and carried out histologic review, methylation profiling, and custom panel, genome, or exome sequencing. After excluding tumors representing other established entities or subgroups, we identified 130 cases to be part of an “intrinsic” spectrum of disease specific to the infant population. These included those with targetable MAPK alterations, and a large proportion of remaining cases harboring gene fusions targeting ALK (n = 31), NTRK1/2/3 (n = 21), ROS1 (n = 9), and MET (n = 4) as their driving alterations, with evidence of efficacy of targeted agents in the clinic. These data strongly support the concept that infant gliomas require a change in diagnostic practice and management.

• Lundar, Tryggve; Due-Tønnessen, Bernt Johan; Fric, Radek; Brandal, Petter & Due-Tønnessen, Paulina (2020). Adult outcome after treatment of pediatric posterior fossa ependymoma: long-term follow-up of a single consecutive institutional series of 22 patients with more than 5 years of survival. Journal of Neurosurgery: Pediatrics. ISSN 1933-0707. 26(1), p. 22–26. doi: 10.3171/2020.1.PEDS19700. Full text in Research Archive
• Larsson, Christopher; Groote, Inge Rasmus; Vardal, Jonas; Kleppestø, Magne Mørk; Odland, Audun & Brandal, Petter [Show all 13 contributors for this article] (2020). Prediction of survival and progression in glioblastoma patients using temporal perfusion changes during radiochemotherapy. Magnetic Resonance Imaging. ISSN 0730-725X. 68, p. 106–112. doi: 10.1016/j.mri.2020.01.012. Full text in Research Archive Show summary

  Background The aim of this study was to investigate changes in structural magnetic resonance imaging (MRI) according to the RANO criteria and perfusion- and permeability related metrics derived from dynamic contrast-enhanced MRI (DCE) and dynamic susceptibility contrast MRI (DSC) during radiochemotherapy for prediction of progression and survival in glioblastoma. Methods Twenty-three glioblastoma patients underwent biweekly structural and perfusion MRI before, during, and two weeks after a six weeks course of radiochemotherapy. Temporal trends of tumor volume and the perfusion-derived parameters cerebral blood volume (CBV) and blood flow (CBF) from DSC and DCE, in addition to contrast agent capillary transfer constant (Ktrans) from DCE, were assessed. The patients were separated in two groups by median survival and differences between the two groups explored. Clinical- and MRI metrics were investigated using univariate and multivariate survival analysis and a predictive survival index was generated. Results Median survival was 19.2 months. A significant decrease in contrast-enhancing tumor size and CBV and CBF in both DCE- and DSC-derived parameters was seen during and two weeks past radiochemotherapy (p < 0.05). A 10%/30% increase in Ktrans/CBF two weeks after finishing radiochemotherapy resulted in significant shorter survival (13.9/16.8 vs. 31.5/33.1 months; p < 0.05). Multivariate analysis revealed an index using change in Ktrans and relative CBV from DSC significantly corresponding with survival time in months (r2 = 0.843; p < 0.001). Conclusions Significant temporal changes are evident during radiochemotherapy in tumor size (after two weeks) and perfusion-weighted MRI-derived parameters (after four weeks) in glioblastoma patients. While DCE-based metrics showed most promise for early survival prediction, a multiparametric combination of both DCE- and DSC-derived metrics gave additional information.

• Rahman, Mohummad Aminur; Brekke, Jorunn; Arnesen, Victoria Smith; Hannisdal, Marianne Hjellvik; Navarro, Andrea Gras & Waha, Andreas [Show all 17 contributors for this article] (2020). Sequential bortezomib and temozolomide treatment promotes immunological responses in glioblastoma patients with positive clinical outcomes: A phase 1B study. Immunity,Inflammation and Disease. 8(3), p. 342–359. doi: 10.1002/iid3.315. Full text in Research Archive Show summary

  Background Glioblastoma (GBM) is an aggressive malignant brain tumor where median survival is approximately 15 months after best available multimodal treatment. Recurrence is inevitable, largely due to O6 methylguanine DNA methyltransferase (MGMT) that renders the tumors resistant to temozolomide (TMZ). We hypothesized that pretreatment with bortezomib (BTZ) 48 hours prior to TMZ to deplete MGMT levels would be safe and tolerated by patients with recurrent GBM harboring unmethylated MGMT promoter. The secondary objective was to investigate whether 26S proteasome blockade may enhance differentiation of cytotoxic immune subsets to impact treatment responses measured by radiological criteria and clinical outcomes. Methods Ten patients received intravenous BTZ 1.3 mg/m2 on days 1, 4, and 7 during each 4th weekly TMZ‐chemotherapy starting on day 3 and escalated from 150 mg/m2 per oral 5 days/wk via 175 to 200 mg/m2 in cycles 1, 2, and 3, respectively. Adverse events and quality of life were evaluated by CTCAE and EQ‐5D‐5L questionnaire, and immunological biomarkers evaluated by flow cytometry and Luminex enzyme‐linked immunosorbent assay. Results Sequential BTZ + TMZ therapy was safe and well tolerated. Pain and performance of daily activities had greatest impact on patients' self‐reported quality of life and were inversely correlated with Karnofsky performance status. Patients segregated a priori into three groups, where group 1 displayed stable clinical symptoms and/or slower magnetic resonance imaging radiological progression, expanded CD4+ effector T‐cells that attenuated cytotoxic T‐lymphocyte associated protein‐4 and PD‐1 expression and secreted interferon γ and tumor necrosis factor α in situ and ex vivo upon stimulation with PMA/ionomycin. In contrast, rapidly progressing group 2 patients exhibited tolerised T‐cell phenotypes characterized by fourfold to sixfold higher interleukin 4 (IL‐4) and IL‐10 Th‐2 cytokines after BTZ + TMZ treatment, where group 3 patients exhibited intermediate clinical/radiological responses. Conclusion Sequential BTZ + TMZ treatment is safe and promotes Th1‐driven immunological responses in selected patients with improved clinical outcomes (Clinicaltrial.gov (NCT03643549)).

• Lundar, Tryggve; Due-Tønnessen, Bernt Johan; Frič, Radek; Brandal, Petter; Stensvold, Einar & Due-Tønnessen, Paulina (2020). Outcomes in adulthood after neurosurgical treatment of brain tumors in the first 3 years of life: long-term follow-up of a single consecutive institutional series of 97 patients. Child's Nervous System. ISSN 0256-7040. 37, p. 427–433. doi: 10.1007/s00381-020-04859-1. Full text in Research Archive Show summary

  Abstract Background Long-term outcome for children who underwent surgery for brain tumors in the first 3 years of life is not well-known. Methods We performed a retrospective study on surgical morbidity, mortality rate, academic achievement, and work participation in children below 3 years of age who underwent primary tumor resection for a brain tumor in the period from 1973 to 1998. Gross motor function and activities of daily life were scored according to the Barthel Index. Long-term survivors were defined as with a survival from primary diagnosis of 20 years or more. Findings Ninety-seven consecutive children were included. No patient was lost to follow-up. Gross total resection was achieved in 67 children during the primary procedure, 25 had subtotal resections, and 5 had only partial resection. The 20-year survival figures for the 46 children with high-grade tumors was 33%, and the corresponding figures for 51 patients treated for low-grade tumors was 82%. Five of the 57 20-year-survivors died 21, 29, 30, 30, and 41 years, respectively, following primary surgery. Fifty of the 52 long-term survivors had a Barthel Index (BI) of 100, while the remaining two had a BI of 40. Twelve patients were long-term survivors after treatment for HG tumors (26%), while 40 of the 51 patients treated for LG tumors (78%) were alive. Thirty-two of the 52 long-term survivors were in full-time work and 29 of them after treatment for LG tumors. Another 10 were in part-time work, while the last 10 individuals had no working capacity. Conclusion Survival is better for patients with low-grade tumors compared with those with high-grade tumors. The functional level of long-term survivors is affected by adjuvant therapy and radiotherapy in particular. Neurosurgical intervention in itself is safe and plausible for pediatric brain tumor patients below 3 years of age. However, there should be a focus on potential late affects, and survivors should be followed by knowledgeable clinical staff for the neoplastic disease as well as for potential side effects. In this consecutive series, a 33% 20-year survival for children treated for HG tumors and 82% for patients with LG tumors was observed. The patients with LG tumors who had been treated with surgical resection without any adjuvant therapy showed a good clinical outcome as adults, and two-thirds of them were in full-time work.

• Kierulf-Vieira, Kirsten Strømme; Sandberg, Cecilie; Waaler, Jo; Lund, Kaja; Skaga, Erlend & Saberniak, Birthe Mikkelsen [Show all 11 contributors for this article] (2020). A small-molecule tankyrase inhibitor reduces glioma stem cell proliferation and sphere formation. Cancers. 12(6), p. 1–16. doi: 10.3390/cancers12061630. Full text in Research Archive Show summary

  Evidence suggests that the growth and therapeutic resistance of glioblastoma (GBM) may be enabled by a population of glioma stem cells (GSCs) that are regulated by typical stem cell pathways, including the WNT/β-catenin signaling pathway. We wanted to explore the effect of treating GSCs with a small-molecule inhibitor of tankyrase, G007-LK, which has been shown to be a potent modulator of the WNT/β-catenin and Hippo pathways in colon cancer. Four primary GSC cultures and two primary adult neural stem cell cultures were treated with G007-LK and subsequently evaluated through the measurement of growth characteristics, as well as the expression of WNT/β-catenin and Hippo signaling pathway-related proteins and genes. Treatment with G007-LK decreased in vitro proliferation and sphere formation in all four primary GSC cultures in a dose-dependent manner. G007-LK treatment altered the expression of key downstream WNT/β-catenin and Hippo signaling pathway-related proteins and genes. Finally, cotreatment with the established GBM chemotherapeutic compound temozolomide (TMZ) led to an additive reduction in sphere formation, suggesting that WNT/β-catenin signaling may contribute to TMZ resistance. These observations suggest that tankyrase inhibition may serve as a supplement to current GBM therapy, although more work is needed to determine the exact downstream mechanisms involved.

• Stensvold, Einar; Stadskleiv, Kristine; Myklebust, Tor Åge; Wesenberg, Finn; Helseth, Eirik & Bechensteen, Anne Grete [Show all 7 contributors for this article] (2020). Unmet rehabiliation needs in 86% of Norwegian paediatric embryonal brain tumour survivors. Acta Paediatrica. ISSN 0803-5253. 109(9), p. 1875–1886. doi: 10.1111/apa.15188. Full text in Research Archive Show summary

  Aim To study incidence, types and degrees of late effects in a geographical cohort of paediatric medulloblastoma and central nervous system primitive neuroectodermal tumour (CNS‐PNET) survivors, and identify the need for rehabilitation. Methods Between 1974 and 2013, 63 patients survived treatment for paediatric medulloblastoma and CNS‐PNET at Oslo University Hospital, Norway. Of these, 50 accepted invitation and were included in this study. Results Median follow‐up was 20 years (range 3.2‐41), and 96% of participants had developed late effects. Cognitive impairment was found in 72%, reduced hearing in 68%, endocrine deficits in 66%, epilepsy in 32% and another 30% had been diagnosed with one or more second primary neoplasms. Radiotherapy significantly increased risk of secondary primary neoplasms and endocrinological deficits, chemotherapy risk of ototoxicity and endocrinological deficits, and epilepsy was found significantly more often in CNS‐PNET than medulloblastoma patients. Epilepsy was the main cause of cognitive impairments (full‐scale IQ) in our study. 86% of participants had an unmet rehabilitation need. Conclusion Significant late effects and unmet rehabilitation needs were documented in the large majority of survivors after treatment for paediatric medulloblastoma and CNS‐PNET.

• Jeanmougin, Marine; Håvik, Annette Bentsen; Cekaite, Lina; Brandal, Petter; Sveen, Anita & Meling, Torstein Ragnar [Show all 11 contributors for this article] (2020). Improved prognostication of glioblastoma beyond molecular subtyping by transcriptional profiling of the tumor microenvironment. Molecular Oncology. ISSN 1574-7891. p. 1016–1027. doi: 10.1002/1878-0261.12668. Full text in Research Archive Show summary

  Glioblastoma (GBM), the most aggressive form of brain cancer, is characterized by a high level of molecular heterogeneity, and infiltration by various immune and stromal cell populations. Important advances have been made in deciphering the microenvironment of GBMs, but its association with existing molecular subtypes and its potential prognostic role remain elusive. We have investigated the abundance of infiltrating immune and stromal cells in silico, from gene expression profiles. Two cohorts, including in‐house normal brain and glioma samples (n = 70) and a large sample set from TCGA (n = 393), were combined into a single exploratory dataset. A third independent cohort (n = 124) was used for validation. Tumors were clustered based on their microenvironment infiltration profiles, and associations with known GBM molecular subtypes and patient outcome were tested a posteriori in a multivariable setting. We identified a subset of GBM samples with significantly higher abundances of most immune and stromal cell populations. This subset showed increased expression of both immune suppressor and immune effector genes compared to other GBMs and was enriched for the mesenchymal molecular subtype. Survival analyses suggested that tumor microenvironment infiltration pattern was an independent prognostic factor for GBM patients. Among all, patients with the mesenchymal subtype with low immune and stromal infiltration had the poorest survival. By combining molecular subtyping with gene expression measures of tumor infiltration, the present work contributes with improving prognostic models in GBM.

• Stadskleiv, Kristine; Stensvold, Einar; Stokka, Kjersti; Bechensteen, Anne Grete & Brandal, Petter (2020). Neuropsychological functioning in survivors of childhood medulloblastoma/CNS-PNET: The role of secondary medical complications. The Clinical Neuropsychologist. ISSN 1385-4046. doi: 10.1080/13854046.2020.1794045. Full text in Research Archive Show summary

  To investigate the long-term cognitive consequences of malignant pediatric brain tumor and its treatment, and factors explaining variability in cognitive functioning among survivors. Method: A geographical cohort of survivors of pediatric medulloblastoma (MB) and supratentorial primitive neuroectodermal tumor (CNS-PNET), treated between 1974 and 2013, was invited to participate. Of the 63 surviving patients, 50 (79%) consented to participation. The participants were tested with a battery of neuropsychological tests covering a wide age range. Verbal cognition, nonverbal cognition, processing speed, attention, memory, executive functioning, and manual dexterity were assessed. The participants were between 5:5 and 51:11 years of age at time of assessment. Assessments took place on average 19 years after primary tumor resective surgery. Results: One participant had a severe intellectual disability. For the rest, IQ varied from 52 to 125, with a mean score of 88.0 (SD 19.7). Twenty-eight (56%) of the participants had full-scale IQ scores in the age-average range or above. Gender, age at operation, time since operation, the presence of secondary medical complications, and treatment variables explained 46% of the variability in IQ scores, F(4,44) =  9.5, p<.001. The presence of endocrine insufficiency in combination with either epilepsy and/or hydrocephalus was associated with lowered IQ, lowered processing speed, and memory impairments. Conclusion: Patients treated for childhood MB and CNS-PNET have a lifelong risk of medical sequelae, including impaired cognitive functioning. This study adds to the literature by demonstrating the importance of following neuropsychological functioning closely, especially processing speed, learning, and memory, in survivors who have multiple secondary medical complications.

• Frič, Radek; Due-Tønnessen, Bernt Johan; Lundar, Tryggve; Egge, Arild; Krossnes, Bård Kronen & Due-Tønnessen, Paulina [Show all 8 contributors for this article] (2020). Long-term outcome of posterior fossa medulloblastoma in patients surviving more than 20 years following primary treatment in childhood. Scientific Reports. 10:9371, p. 1–7. doi: 10.1038/s41598-020-66328-8. Full text in Research Archive Show summary

  The aim of the study was to analyze the long-term outcome (>20 years) after treatment of posterior fossa medulloblastoma (MB) in childhood. We analyzed data from patients treated for posterior fossa MB between 1974 (introduction of the first international treatment protocol in Norway) and 1987 (when use of radiotherapy was abandoned in children under 4 years of age). Out of 47 children, 24 survived >20 years. At the time of analysis, 16 patients (median age 41 years, range 32–52) were alive (median follow-up 34 years, range 30–42), while 8 patients died 22–41 years (median 31 years) after primary treatment: one late death (after 22 years) was due to tumor recurrence whilst other 7 deaths (after 23 to 41 years) were related to the detrimental effects of the treatment (secondary tumors, stroke, severe epilepsy and depression). Observed 20- and 30-year survival rates were 51% and 44%, respectively. Despite successful treatment of MB in childhood and satisfactory tumor control during the first 20 years following primary treatment, our data indicates that even long-term survivors may die from tumor recurrence. However, the main factors causing late mortality and morbidity in long-term survivors seem to be the complications related to radiotherapy given in childhood.

• Stokkevåg, Camilla Hanquist; Indelicato, Daniel J.; Herfarth, Klaus; Magelssen, Henriette; Evensen, Morten Egeberg & Ugland, Maren [Show all 20 contributors for this article] (2019). Normal tissue complication probability models in plan evaluation of children with brain tumors referred to proton therapy. Acta Oncologica. ISSN 0284-186X. 58(10), p. 1416–1422. doi: 10.1080/0284186X.2019.1643496. Full text in Research Archive Show summary

  Background: Children with brain tumors undergoing radiotherapy are at particular risk of radiation-induced morbidity and are therefore routinely considered for proton therapy (PT) to reduce the dose to healthy tissues. The aim of this study was to apply pediatric constraints and normal tissue complication probability (NTCP) models when evaluating the differences between PT and contemporary photon-based radiotherapy, volumetric modulated arc therapy (VMAT). Methods: Forty patients (aged 1–17 years) referred from Norwegian institutions to cranial PT abroad during 2014–2016 were selected for VMAT re-planning using the original CT sets and target volumes. The VMAT and delivered PT plans were compared by dose/volume metrics and NTCP models related to growth hormone deficiency, auditory toxicity, visual impairment, xerostomia, neurocognitive outcome and secondary brain and parotid gland cancers. Results: The supratentorial brain, temporal lobes, hippocampi, hypothalamus, pituitary glands, cochleas, salivary glands, optic nerves and chiasm received lower mean doses from PT. Reductions in population median NTCP were significant for auditory toxicity (VMAT: 3.8%; PT: 0.3%), neurocognitive outcome (VMAT: 3.0 IQ points decline at 5 years post RT; PT: 2.5 IQ points), xerostomia (VMAT: 2.0%; PT: 0.6%), excess absolute risk of secondary cancer of the brain (VMAT: 9.2%; PT: 6.7%) and salivary glands (VMAT: 2.8%; PT:0.5%). Across all patients, 23/38 PT plans had better or comparable estimated risks for all endpoints (within ±10% of the risk relative to VMAT), whereas for 1/38 patients all estimates were better or comparable with VMAT. Conclusions: PT reduced the volumes of normal tissues exposed to radiation, particularly low-to-intermediate dose levels, and this was reflected in lower NTCP. Of the included endpoints, substantial reductions in population medians were seen from the delivered PT plans for auditory complications, xerostomia, and risk of secondary cancers of the brain and salivary glands.

• Latysheva, Anna; Emblem, Kyrre Eeg; Brandal, Petter; Vik-Mo, Einar O.; Pahnke, Jens & Røysland, Kjetil [Show all 8 contributors for this article] (2019). Dynamic susceptibility contrast and diffusion MR imaging identify oligodendroglioma as defined by the 2016 WHO classification for brain tumors: histogram analysis approach. Neuroradiology. ISSN 0028-3940. 61(5), p. 545–555. doi: 10.1007/s00234-019-02173-5. Full text in Research Archive Show summary

  Purpose According to the revised World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS) of 2016, oligodendrogliomas are now defined primarily by a specific molecular signature (presence of IDH mutation and 1p19q codeletion). The purpose of our study was to assess the value of dynamic susceptibility contrast MR imaging (DSC-MRI) and diffusion-weighted imaging (DWI) to characterize oligodendrogliomas and to distinguish them from astrocytomas. Methods Seventy-one adult patients with untreated WHO grade II and grade III diffuse infiltrating gliomas and known 1p/19q codeletion status were retrospectively identified and analyzed using relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) maps based on whole-tumor volume histograms. The Mann-Whitney U test and logistic regression were used to assess the ability of rCBV and ADC to differentiate between oligodendrogliomas and astrocytomas both independently, but also related to the WHO grade. Prediction performance was evaluated in leave-one-out cross-validation (LOOCV). Results Oligodendrogliomas showed significantly higher microvascularity (higher rCBVMean ≥ 0.80, p = 0.013) and higher vascular heterogeneity (lower rCBVPeak ≤ 0.044, p = 0.015) than astrocytomas. Diffuse gliomas with higher cellular density (lower ADCMean ≤ 1094 × 10−6 mm2/s, p = 0.009) were more likely to be oligodendrogliomas than astrocytomas. Histogram analysis of rCBV and ADC was able to differentiate between diffuse astrocytomas (WHO grade II) and anaplastic astrocytomas (WHO grade III). Conclusion Histogram-derived rCBV and ADC parameter may be used as biomarkers for identification of oligodendrogliomas and may help characterize diffuse gliomas based upon their genetic characteristics. Keywords Diffuse glioma Perfusion MRI Diffusion MRI

• Stensvold, Einar; Myklebust, Tor Åge; Cappelen, Johan; Due-Tønnessen, Bernt Johan; Due-Tønnessen, Paulina & Kepka, Aleksandra [Show all 24 contributors for this article] (2019). Children treated for medulloblastoma and supratentorial primitive neuroectodermal tumor in Norway from 1974 through 2013: Unexplainable regional differences in survival. Pediatric Blood & Cancer. ISSN 1545-5009. 66:e27910(10), p. 1–12. doi: 10.1002/pbc.27910. Full text in Research Archive Show summary

  Background A previous study based on Norwegian Cancer Registry data suggested regional differences in overall survival (OS) after treatment for medulloblastoma (MB) and supratentorial primitive neuroectodermal tumor (CNS‐PNET) in Norway. The purpose of the present study was to confirm in an extended cohort whether there were regional differences in outcome or not, and if so try to identify possible explanations. Material and methods Data from patients aged 0–20 years diagnosed with and treated for MB/CNS‐PNET at all four university hospitals in Norway from 1974 to 2013 were collected and compared. Results Of 266 identified patients, 251 fulfilled inclusion criteria. MB was diagnosed in 200 and CNS‐PNET in 51 patients. Five‐year OS and event‐free survival (EFS) were 59% and 52%, respectively. There was a significant difference in five‐year OS and EFS between MB and CNS‐PNET patients; 62% versus 47% (P = 0.007) and 57% versus 35% (P < 0.001). In multivariable analysis, two factors were found to significantly contribute to improved five‐year OS and EFS, whereas one factor contributed to improved five‐year OS only. Gross total resection (GTR) versus non‐GTR (hazard ratio [HR] 0.53, P = 0.003; HR 0.46, P < 0.001) and cerebrospinal irradiation (CSI) versus non‐CSI (HR 0.24, P < 0.001; HR 0.28, P < 0.001) for both, and treatment outside Oslo University Hospital for OS only (HR 0.64, P = 0.048). Conclusion Survival was comparable with data from other population‐based studies, and the importance of GTR and CSI was confirmed. The cause for regional survival differences could not be identified.

• Bogsrud, Trond; Løndalen, Ayca; Brandal, Petter; Leske, Henning; Panagopoulos, Ioannis & Borghammer, Per [Show all 7 contributors for this article] (2019). 18F-Fluciclovine PET/CT in Suspected Residual or Recurrent High-Grade Glioma. Clinical Nuclear Medicine. ISSN 0363-9762. 44(8), p. 605–611. doi: 10.1097/RLU.0000000000002641. Full text in Research Archive
• Lundar, Tryggve; Due-Tønnessen, Bernt Johan; Frič, Radek; Krossnes, Bård Kronen; Brandal, Petter & STENSVOLD, EINAR [Show all 7 contributors for this article] (2019). Neurosurgical treatment of pediatric pleomorphic xanthoastrocytomas: Long-term follow-up of a single-institution, consecutive series of 12 patients. Journal of Neurosurgery: Pediatrics. ISSN 1933-0707. 23(4), p. 512–516. doi: 10.3171/2018.11.PEDS18449. Full text in Research Archive
• Lundar, Tryggve; Due-Tønnessen, Bernt Johan; Frič, Radek; Brandal, Petter; Stensvold, Einar & Due-Tønnessen, Paulina (2019). Adult outcome after neurosurgical treatment of brain tumours in the first year of life: long-term follow-up of a single consecutive institutional series of 34 patients. Acta Neurochirurgica. ISSN 0001-6268. 161(9), p. 1793–1798. doi: 10.1007/s00701-019-04014-z. Full text in Research Archive Show summary

  Background Long-term results for adult patients who underwent surgery for paediatric brain tumours in the first year of life have not been reported. Methods We performed a retrospective study on surgical morbidity, mortality rate, academic achievement and/or work participation in patients who underwent primary tumour resection for a brain tumour as infants in the period from 1973 to 1998. Gross motor function and activities of daily life were scored according to the Barthel Index. Findings Thirty-four consecutive children were included. No patient was lost to follow-up. Twenty-two children (65%) underwent gross total resection (GTR), 10 had subtotal resections (STR) and 2 had only partial resection during primary surgery. Nine children were additionally surgically treated for hydrocephalus (HC), many of them with repeat operations for shunt malfunction during follow-up. Three children died within 30 days following GTR of highly vascular tumours. Seventeen (50%) of the infants had high-grade tumours with 1-month, 1-year and 20-year survival figures of 88, 30 and 30%. The corresponding figures for 17 patients treated for low-grade tumours were 94%, 88% and 88%, respectively. Seventeen patients (50%) are still alive as adult long-term survivors at median age of 29 years (range 20 to 43 years). Three died after 29, 30 and 41 years, respectively. At the latest follow-up, 16 out of 17 long-term survivors have a Barthel Index (BI) of 100, while the remaining one has a BI of 40. Two long-term survivors of a high-grade tumour treated 30 and 35 years ago are severely handicapped and have no working capacity. The 15 long-term survivors after treatment for a low-grade tumour are all in daily activity as students (4), in part-time work (3) or full-time work (8). Conclusion A brain tumour occurring in the first year of life is a serious threat to the patient and the family, particularly in case of high-grade tumours. In our small cohort, the results from long-term survivors of high-grade tumour group are depressing and confirm the deleterious effect of radiotherapy given to infants decades ago. The infants with low-grade tumours who could be treated with surgical resection without any adjuvant therapy show a good clinical outcome as adults. For parents of these latter patients, the results are far better than feared in advance

• Bjune, Katrine; Høyer, Ellen; Schanke, Anne-Kristine & Brandal, Petter (2019). Behov for rehabilitering etter hjernesvulst. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 139(10), p. 1–3. doi: 10.4045/tidsskr.19.0268. Full text in Research Archive
• Lundar, Tryggve; Due-Tønnessen, Bernt Johan; Frič, Radek; Egge, Arild; Krossnes, Bård Kronen & Due-Tønnessen, Paulina [Show all 8 contributors for this article] (2018). Neurosurgical treatment of gangliogliomas in children and adolescents: long-term follow-up of a single-institution series of 32 patients. Acta Neurochirurgica. ISSN 0001-6268. 160(6), p. 1207–1214. doi: 10.1007/s00701-018-3550-8. Full text in Research Archive Show summary

  Object The object of this study was to delineate long-term results of the surgical treatment of pediatric tumors classified as ganglioglioma or gangliocytoma. Methods A cohort of consecutive patients 19 years or younger who had undergone primary resection of CNS tumors during the years 1980–2016 at a single institution were reviewed in this retrospective study of surgical morbidity, mortality, and academic achievement and/or work participation. Gross motor function and activities of daily living were scored using the Barthel Index (BI). Results Patient records for 32 consecutive children and adolescents who had undergone resection for a ganglioglioma were included in this study. Of the 32 patients, 13 were in the first decade at the first surgery, whereas 19 were in the second decade. The male/female ratio was 1.0 (16/16). No patient was lost to follow-up. The tumor was localized to the supratentorial compartment in 26 patients, to the posterior fossa in 5 patients, and to the spinal cord in 1 patient. Only two of the tumors were classified as anaplastic. Of the 30 low-grade tumors, 2 were classified as gangliocytomas, 6 were desmoplastic infantile gangliogliomas, and 22 were ordinary gangliogliomas. The aim of primary surgery was gross-total resection (GTR) and was achieved in 23 patients (71.9%). Altogether, 43 tumor resections were performed. Eight patients underwent a second resection from 1 to 10 years after primary surgery and three of these also had a third resection from 2 to 24 years after initial surgery. The reason for further resection was clinical (seizure control failure/recurrence of epilepsy or progressive neurological deficit) and/or residual tumor progression/recurrence. There was no operative mortality in this series and all 32 patients are alive with follow-up periods from 0.5 to 36 years (median 14 years). Observed 14-year survival is thus 100%. One out of two children with primary anaplastic tumor received local radiotherapy (proton) postoperatively. The other 31 patients did not have any kind of non-surgical adjuvant therapy. Twenty-one out of 26 children with supratentorial tumor had epilepsy as one of their presenting symptoms. Nineteen of these became seizure-free after initial surgery (18 of them after GTR), but 3 patients experienced recurrence of seizures within some years. Functional outcome in terms of ADL, schooling, and work participation was gratifying in most patients. Five patients have persistent hydrocephalus (HC), treated with ventriculoperitoneal (VP) shunts. Conclusion Low-grade gangliogliomas (GGs) can be surgically treated with good long-term results including seizure and tumor control as well as school and working participation.

• Panagopoulos, Ioannis; Gorunova, Ludmila; Leske, Henning; Niehusmann, Pitt; Johannessen, Lene Elisabeth & Staurseth, Julie [Show all 11 contributors for this article] (2018). Pyrosequencing analysis of MGMT promoter methylation in meningioma. Cancer Genomics & Proteomics. ISSN 1109-6535. 15(5), p. 379–385. doi: 10.21873/cgp.20096. Full text in Research Archive Show summary

  Background: Methylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter is a well-established predictor of response to the DNA-alkylating agent temozolomide in patients with glioblastoma. Materials and Methods: Pyrosequencing analysis was used to determine the MGMT promoter methylation status in 61 meningiomas, to clarify whether it might have a predictive role. Results: Only two tumors (3%) had a mean methylation frequency higher than the cut-off value of 10% for the four CpG sites examined. Conclusion: The methylation of the MGMT promoter is uncommon, or occurs at a low frequency in meningiomas. There is no convincing rationale to test such tumors for their MGMT methylation status in a clinical setting.

• Latysheva, Anna; Emblem, Kyrre Eeg; Server, Andrés; Brandal, Petter; Meling, Torstein Ragnar & Pahnke, Jens [Show all 7 contributors for this article] (2018). Survival associations using perfusion and diffusion magnetic resonance imaging in patients with histologic and genetic defined diffuse glioma World Health Organization grades II and III. Journal of computer assisted tomography. ISSN 0363-8715. 42(5), p. 807–815. doi: 10.1097/RCT.0000000000000742. Full text in Research Archive Show summary

  Objective: According to the new World Health Organization 2016 classification for tumors of the central nervous system, 1p/19q codeletion defines the genetic hallmark that differentiates oligodendrogliomas from diffuse astrocytomas. The aim of our study was to evaluate whether relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) histogram analysis can stratify survival in adult patients with genetic defined diffuse glioma grades II and III. Methods: Sixty-seven patients with untreated diffuse gliomas World Health Organization grades II and III and known 1p/19q codeletion status were included retrospectively and analyzed using ADC and rCBV maps based on whole-tumor volume histograms. Overall survival and progression-free survival (PFS) were analyzed by using Kaplan-Meier and Cox survival analyses adjusted for known survival predictors. Results: Significant longer PFS was associated with homogeneous rCBV distribution–higher rCBVpeak (median, 37 vs 26 months; hazard ratio [HR], 3.2; P = 0.02) in patients with astrocytomas, and heterogeneous rCBV distribution–lower rCBVpeak (median, 46 vs 37 months; HR, 5.3; P < 0.001) and higher rCBVmean (median, 44 vs 39 months; HR, 7.9; P = 0.003) in patients with oligodendrogliomas. Apparent diffusion coefficient parameters (ADCpeak, ADCmean) did not stratify PFS and overall survival. Conclusions: Tumors with heterogeneous perfusion signatures and high average values were associated with longer PFS in patients with oligodendrogliomas. On the contrary, heterogeneous perfusion distribution was associated with poor outcome in patients with diffuse astrocytomas.

• Johannessen, Lene Elisabeth; Brandal, Petter; Myklebust, Tor Åge; Heim, Sverre; Micci, Francesca & Panagopoulos, Ioannis (2018). MGMT gene promoter methylation status - Assessment of two pyrosequencing kits and three methylation-specific PCR methods for their predictive capacity in glioblastomas. Cancer Genomics & Proteomics. ISSN 1109-6535. 15(6), p. 437–446. doi: 10.21873/cgp.20102. Full text in Research Archive Show summary

  Background: Although methylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter predicts response to temozolomide in patients with glioblastoma, no consensus exists as to which assay is best for its detection. Materials and Methods: Methylation of MGMT promoter was examined by methylation-specific polymerase chain reaction (MSP), quantitative real-time MSP, methylation-sensitive high-resolution melting analysis, and two commercial pyrosequencing (PSQ) kits. Survival was compared among 48 patients with glioblastoma according to assay results. Results: Only PSQ and MSP significantly separated patients who benefited from temozolomide, with PSQ being the superior method. For PSQ analysis, the cut-off value that best correlated with prognostic outcome was 7% methylation of MGMT. Median survival in patients with MGMT promoter methylation above this cut-off value was 7.8 months longer compared to those with less than 7% methylation. Two-year overall survival for the two groups was 42% and 7.4%, respectively. Conclusion: PSQ is the method of choice for MGMT promoter methylation analysis in routine clinical practice.

• Stensvold, Einar; Krossnes, Bård Kronen; Lundar, Tryggve; Due-Tønnessen, Bernt Johan; Fric, Radek & Due-Tønnessen, Paulina [Show all 10 contributors for this article] (2017). Outcome for children treated for medulloblastoma and supratentorial primitive neuroectodermal tumor (CNS-PNET) - a retrospective analysis spanning 40 years of treatment. Acta Oncologica. ISSN 0284-186X. 56(5), p. 698–705. doi: 10.1080/0284186X.2017.1301679. Full text in Research Archive
• Vandraas, Kathrine; Tjønnfjord, Geir Erland; Johannessen, Tom Børge & Brandal, Petter (2016). Persistent bone marrow depression following short-term treatment with temozolomide. BMJ Case Reports. 2016. doi: 10.1136/bcr-2016-215797. Full text in Research Archive
• Olsen, Thale Kristin; Panagopoulos, Ioannis; Gorunova, Ludmila; Micci, Francesca; Andersen, Kristin & Andersen, Hege Kilen [Show all 11 contributors for this article] (2016). Novel fusion genes and chimeric transcripts in ependymal tumors. Genes, Chromosomes and Cancer. ISSN 1045-2257. 55(12), p. 944–953. doi: 10.1002/gcc.22392. Full text in Research Archive Show summary

  We have previously identified two ALK rearrangements in a subset of ependymal tumors using a combination of cytogenetic data and RNA sequencing. The aim of this study was to perform an unbiased search for fusion transcripts in our entire series of ependymal tumors. Fusion analysis was performed using the FusionCatcher algorithm on 12 RNA-sequenced ependymal tumors. Candidate transcripts were prioritized based on the software's filtering and manual visualization using the BLAST (Basic Local Alignment Search Tool) and BLAT (BLAST-like alignment tool) tools. Genomic and reverse transcriptase PCR with subsequent Sanger sequencing was used to validate the potential fusions. Fluorescent in situ hybridization (FISH) using locus-specific probes was also performed. A total of 841 candidate chimeric transcripts were identified in the 12 tumors, with an average of 49 unique candidate fusions per tumor. After algorithmic and manual filtering, the final list consisted of 24 potential fusion events. Raw RNA-seq read sequences and PCR validation supports two novel fusion genes: a reciprocal fusion gene involving UQCR10 and C1orf194 in an adult spinal ependymoma and a TSPAN4-CD151 fusion gene in a pediatric infratentorial anaplastic ependymoma. Our previously reported ALK rearrangements and the RELA and YAP1 fusions found in supratentorial ependymomas were until now the only known fusion genes present in ependymal tumors. The chimeric transcripts presented here are the first to be reported in infratentorial or spinal ependymomas. Further studies are required to characterize the genomic rearrangements causing these fusion genes, as well as the frequency and functional importance of the fusions. © 2016 Wiley Periodicals, Inc

• Lundar, Tryggve; Due-Tønnessen, Bernt Johan; Egge, Arild; Krossnes, Bård Kronen; STENSVOLD, EINAR & Due-Tønnessen, Paulina [Show all 7 contributors for this article] (2015). Neurosurgical treatment of brain tumors in the first 6 months of life: long-term follow-up of a single consecutive institutional series of 30 patients. Child's Nervous System. ISSN 0256-7040. 31(12), p. 2283–2290. doi: 10.1007/s00381-015-2792-5. Full text in Research Archive Show summary

  Object The aim of this study is to delineate the long-term results for patients going through surgery for pediatric brain tumors in the first 6 months of life. Methods Thirty consecutive children (1–182 days old) who underwent primary resection for a brain tumor during the years 1973–2012 were included in this retrospective study on surgical morbidity, mortality rate, academic achievement, and/or work participation. Gross motor function and activities of daily life were scored according to the Barthel index. Results Of the 30 patients, 11 children had surgery in the first 3 months of life (1 to 88 days) and 19 were aged 3 to 6 months (94–182 days) at the time of surgery. The male/female ratio was 1.0 (15/15). No patients were lost to follow-up. Two patients died in the postoperative period (30 days). Another eight patients died during the follow-up. Twenty patients are alive, with follow-up times from 2 to 38 years, median 13 years. Among the 28 children who survived the primary resection, eight underwent repeat surgery from 6 months to 5 years after the first operation. Two children were operated three times, and one of these also a fourth time. Gross total resection (GTR) was achieved in 20 of the primary resections, subtotal resection (STR) in 6, and in the last 4, only a biopsy or a partial resection was performed. Nine children received adjuvant chemotherapy and three of these also radiotherapy (in the years 1979–1987). Among the 20 survivors, the Barthel index is normal (100) in 18 patients, 40 in one, and 20 in the last one. Eight tumors were located to the posterior fossa, and 22 were supratentorial. Eighteen tumors were histologically low-grade (WHO grade I–II), most of these were plexus papillomas (7) or astrocytomas (7), and 12 were high-grade (WHO grade I I I–IV); PNET/medulloblastomas (6), ependymoma (2), glioblastoma (2), teratoma, and plexus carcinoma. Conclusion Infants with brain tumors may clearly benefit from surgical resection with favorable results even for prolonged periods of time. Ten children died, two of them with prolonged survival for 9 and 29 years. Among the 20 survivors, a stable very long-term result appears obtainable in 18 also when it comes to quality of life. Four of the survivors have been treated for highly malignant tumors with a follow-up of 5, 11, 14, and 26 years. One of our infant patients treated for GBM in 1982, lived for 29 years, however, with a progressive decline in the quality of life probably due to postoperative whole-brain radiation.

• Olsen, Thale Kristin; Panagopoulos, Ioannis; Meling, Torstein Ragnar; Micci, Francesca; Gorunova, Ludmila & Thorsen, Jim [Show all 13 contributors for this article] (2015). Fusion genes with ALK as recurrent partner in ependymoma-like gliomas: A new brain tumor entity? Neuro-Oncology. ISSN 1522-8517. 17(10), p. 1365–1373. doi: 10.1093/neuonc/nov039. Full text in Research Archive
• Lundar, Tryggve; Due-Tønnessen, Bernt Johan; Krossnes, Bård Kronen; Due-Tønnessen, Paulina & Brandal, Petter (2015). Posterior fossa ependymoma in childhood: 60 years event-free survival after partial resection—a case report. Child's Nervous System. ISSN 0256-7040. 31(9), p. 1573–1576. doi: 10.1007/s00381-015-2766-7. Full text in Research Archive
• Due-Tønnessen, Bernt Johan; Egge, Arild; Lundar, Tryggve; Krossnes, Bård Kronen; STENSVOLD, EINAR & Due-Tønnessen, Paulina [Show all 7 contributors for this article] (2015). Posterior fossa ependymoblastoma diagnosed in the second month of life: uneventful 12 years survival after gross total resection followed by chemotherapy. SpringerPlus. 4:389. doi: 10.1186/s40064-015-1178-1. Full text in Research Archive
• Panagopoulos, Ioannis; Brandal, Petter; Gorunova, Ludmila; Bjerkehagen, Bodil & Heim, Sverre (2014). Novel CSF1-S100A10 fusion gene and CSF1 transcript identified by RNA sequencing in tenosynovial giant cell tumors. International Journal of Oncology. ISSN 1019-6439. 44(5), p. 1425–1432. doi: 10.3892/ijo.2014.2326. Full text in Research Archive
• Lundar, Tryggve; Due-Tønnessen, Bernt Johan; Scheie, David & Brandal, Petter (2014). Pediatric spinal ependymomas: an unpredictable and puzzling disease. Long-term follow-up of a single consecutive institutional series of ten patients. Child's Nervous System. ISSN 0256-7040. 30(12), p. 2083–2088. doi: 10.1007/s00381-014-2491-7. Full text in Research Archive
• Lundar, Tryggve; Due-Tønnessen, Bernt Johan; Egge, Arild; Scheie, David; Brandal, Petter & STENSVOLD, EINAR [Show all 7 contributors for this article] (2014). Neurosurgical treatment of pediatric low-grade midbrain tumors: a single consecutive institutional series of 15 patients. Journal of Neurosurgery: Pediatrics. ISSN 1933-0707. 14, p. 598–603. doi: 10.3171/2014.9.PEDS1462. Full text in Research Archive
• Rogne, Siril Gudmundson; Helseth, Eirik; Brandal, Petter; Scheie, David & Meling, Torstein (2014). Are melanomas averse to cerebellum? Cerebellar metastases in a surgical series. Acta Neurologica Scandinavica. ISSN 0001-6314. 130(1), p. 1–10. doi: 10.1111/ane.12206. Full text in Research Archive
• Olsen, Thale Kristin; Gorunova, Ludmila; Meling, Torstein; Micci, Francesca; Scheie, David & Due-Tønnessen, Bernt Johan [Show all 8 contributors for this article] (2014). Genomic characterization of ependymomas reveals 6q loss as the most common aberration. Oncology Reports. ISSN 1021-335X. 32(2), p. 483–490. doi: 10.3892/or.2014.3271. Full text in Research Archive Show summary

  Ependymomas are rare tumors of the central nervous system (CNS). They are classified based on tumor histology and grade, but the prognostic value of the WHO grading system remains controversial. Treatment is mainly surgical and by radiation. An improved knowledge of ependymoma biology is important to elucidate the pathogenesis, to improve classification schemes, and to identify novel potential treatment targets. Only 113 ependymoma karyotypes with chromosome aberrations are registered in the Mitelman database. We present the first study of ependymoma genomes combining karyotyping and high resolution comparative genomic hybridization (HR-CGH). Nineteen tumor samples were collected from three pediatric and 15 adult patients treated at Oslo University Hospital between 2005 and 2012. Histological diagnoses included subependymoma and myxopapillary ependymoma (WHO grade I), ependymoma (WHO grade II) and anaplastic ependymoma (WHO grade III). Four tumors were intraspinal and 15 were intracranial. Seventeen samples were successfully karyotyped, HR-CGH analysis was undertaken on 17 samples, and 15 of 19 tumors were analyzed using both methods. Twelve tumors had karyotypic abnormalities, mostly gains or losses of whole chromosomes. Structural rearrangements were found in four tumors, in two of which 2p23 was identified as a breakpoint region. Twelve tumors displayed genomic imbalances by HR-CGH analysis with loss of material at 6q as the most common. 6q loss, which was detected by one or both methods in seven of 12 (58%) abnormal tumors, and 5p gain (observed in five tumors; 42%) were the most common genomic aberrations in this series.

• Larsson, Christopher; Kleppestø, Magne Mørk; Rasmussen, Inge-André; Salo, Raimo Aleksi; Vardal, Jonas & Brandal, Petter [Show all 7 contributors for this article] (2013). Sampling requirements in DCE-MRI based analysis of high grade gliomas: Simulations and clinical results. Journal of Magnetic Resonance Imaging. ISSN 1053-1807. 37(4), p. 818–829. doi: 10.1002/jmri.23866. Full text in Research Archive
• Panagopoulos, Ioannis; Gorunova, Ludmila; Brandal, Petter; Garnes, Margaret; Tierens, Anne & Heim, Sverre (2013). Myeloid leukemia with t(7;21)(p22;q22) and 5q deletion. Oncology Reports. ISSN 1021-335X. 30(4), p. 1549–1552. doi: 10.3892/or.2013.2623. Full text in Research Archive
• Lundar, Tryggve; Due-Tønnessen, Bernt Johan; Egge, Arild; Scheie, David; STENSVOLD, EINAR & Brandal, Petter (2013). Neurosurgical treatment of oligodendroglial tumors in children and adolescents: a single-institution series of 35 consecutive patients. Journal of Neurosurgery: Pediatrics. ISSN 1933-0707. 12(3), p. 241–246. doi: 10.3171/2013.6.PEDS12586. Full text in Research Archive
• Murrell, Wayne; Palmero, Emily Herrera; Bianco, John; Stangeland, Biljana; Joel, Mrinal & Paulson, Linda Marie [Show all 16 contributors for this article] (2013). Expansion of Multipotent Stem Cells from the Adult Human Brain. PLOS ONE. 8(8). doi: 10.1371/journal.pone.0071334. Full text in Research Archive
• Håvik, Annette Bentsen; Brandal, Petter; Honne, Hilde; Dahlback, Hanne-Sofie Spenning; Scheie, David & Hektoen, Merete [Show all 11 contributors for this article] (2012). MGMT promoter methylation in gliomas-assessment by pyrosequencing and quantitative methylation-specific PCR. Journal of Translational Medicine. 10. doi: 10.1186/1479-5876-10-36. Full text in Research Archive Show summary

  Background Methylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter is a favorable prognostic factor in glioblastoma patients. However, reported methylation frequencies vary significantly partly due to lack of consensus in the choice of analytical method. Method We examined 35 low- and 99 high-grade gliomas using quantitative methylation specific PCR (qMSP) and pyrosequencing. Gene expression level of MGMT was analyzed by RT-PCR. Results When examined by qMSP, 26% of low-grade and 37% of high-grade gliomas were found to be methylated, whereas 97% of low-grade and 55% of high-grade gliomas were found methylated by pyrosequencing. The average MGMT gene expression level was significantly lower in the group of patients with a methylated promoter independent of method used for methylation detection. Primary glioblastoma patients with a methylated MGMT promoter (as evaluated by both methylation detection methods) had approximately 5 months longer median survival compared to patients with an unmethylated promoter (log-rank test; pyrosequencing P = .02, qMSP P = .06). One third of the analyzed samples had conflicting methylation results when comparing the data from the qMSP and pyrosequencing. The overall survival analysis shows that these patients have an intermediate prognosis between the groups with concordant MGMT promoter methylation results when comparing the two methods. Conclusion In our opinion, MGMT promoter methylation analysis gives sufficient prognostic information to merit its inclusion in the standard management of patients with high-grade gliomas, and in this study pyrosequencing came across as the better analytical method.

• Dahlback, Hanne-Sofie Spenning; Gorunova, Ludmila; Micci, Francesca; Scheie, David; Brandal, Petter & Meling, Torstein [Show all 7 contributors for this article] (2011). Molecular Cytogenetic Analysis of a Gliosarcoma with Osseous Metaplasia. Cytogenetic and Genome Research. ISSN 1424-8581. 134(2), p. 88–95. doi: 10.1159/000326804. Full text in Research Archive
• Dahlback, Hanne-Sofie Spenning; Gorunova, Ludmila; Brandal, Petter; Scheie, David; Helseth, Eirik & Meling, Torstein [Show all 7 contributors for this article] (2011). Genomic Aberrations in Diffuse Low-Grade Gliomas. Genes, Chromosomes and Cancer. ISSN 1045-2257. 50(6), p. 409–420. doi: 10.1002/gcc.20866. Full text in Research Archive
• Dahlback, Hanne-Sofie Spenning; Brandal, Petter; Krossnes, Bård Kronen; Fric, Radek; Meling, Torstein & Meza, Leonardo Zepeda [Show all 8 contributors for this article] (2011). Multiple chromosomal monosomies are characteristic of giant cell ependymoma. Human Pathology. ISSN 0046-8177. 42(12), p. 2042–2046. doi: 10.1016/j.humpath.2011.02.012. Full text in Research Archive
• Kyriazoglou, Anastasios I; Dimitriadis, Efthimios; Arnogiannaki, Niki; Brandal, Petter; Heim, Sverre & Pandis, Nikos (2011). Similar cytogenetic findings in two synchronous secondary peripheral chondrosarcomas in a patient with multiple osteochondromas. Cancer Genetics. ISSN 2210-7762. 204(12), p. 677–681. doi: 10.1016/j.cancergen.2011.10.013. Full text in Research Archive
• Dahlback, Hanne-Sofie Spenning; Brandal, Petter; Gorunova, Ludmila; Widing, Eva; Meling, Torstein & Krossnes, Bård Kronen [Show all 7 contributors for this article] (2011). Genomic Aberrations in Pediatric Gliomas and Embryonal Tumors. Genes, Chromosomes and Cancer. ISSN 1045-2257. 50(10), p. 788–799. doi: 10.1002/gcc.20898. Full text in Research Archive
• Vik-Mo, Einar O.; Sandberg, Cecilie; Ølstørn, Håvard; Varghese, Mercy; Brandal, Petter & Ramm-Pettersen, Jon-Terje [Show all 8 contributors for this article] (2010). Brain tumor stem cells maintain overall phenotype and tumorigenicity after in vitro culturing in serum-free conditions. Neuro-Oncology. ISSN 1522-8517. 12(12), p. 1220–1230. doi: 10.1093/neuonc/noq102. Full text in Research Archive
• Brandal, Petter; Teixeira, Manuel & Heim, Sverre (2010). Genotypic and Phenotypic Classification of Cancer: How Should the Impact of the Two Diagnostic Approaches Best be Balanced? Genes, Chromosomes and Cancer. ISSN 1045-2257. 49(9), p. 763–774. doi: 10.1002/gcc.20792. Full text in Research Archive
• Brandal, Petter; Bjerkehagen, Bodil; Bruland, Øyvind; Skjeldal, Sigmund; Bogsrud, Trond Velde & Hall, Kirsten Sundby (2009). Synchronous and metachronous skeletal osteosarcomas: The Norwegian Radium Hospital experience. Acta Oncologica. ISSN 0284-186X. 48(8), p. 1165–1172. doi: 10.3109/02841860903032809. Full text in Research Archive
• Brandal, Petter; Panagopoulos, Ioannis; Bjerkehagen, Bodil & Heim, Sverre (2009). t(19;22)(q13;q12) Translocation Leading to the Novel Fusion Gene EWSRI-ZNF444 in Soft Tissue Myoepithelial Carcinoma. Genes, Chromosomes and Cancer. ISSN 1045-2257. 48(12), p. 1051–1056. doi: 10.1002/gcc.20706. Full text in Research Archive
• Dahlback, Hanne-Sofie Spenning; Brandal, Petter; Meling, Torstein; Gorunova, Ludmila; Scheie, David & Heim, Sverre (2009). Genomic Aberrations in 80 Cases of Primary Glioblastoma Multiforme: Pathogenetic Heterogeneity and Putative Cytogenetic Pathways. Genes, Chromosomes and Cancer. ISSN 1045-2257. 48(10), p. 908–924. doi: 10.1002/gcc.20690. Full text in Research Archive
• Brandal, Petter; Panagopoulos, Ioannis; Bjerkehagen, Bodil; Gorunova, Ludmila; Skjeldal, Sigmund & Micci, Francesca [Show all 7 contributors for this article] (2008). Detection of a t(1;22)(q23;q 12) translocation leading to an EWSR1-PBX1 fusion gene in a myoepithelioma. Genes, Chromosomes and Cancer. ISSN 1045-2257. 47, p. 558–564. doi: 10.1002/gcc.20559. Full text in Research Archive

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• Heggebø, Liv Cathrine; Borgen, Ida Maria Henriksen; Blakstad, Hanne Kristin; Saxhaug, Cathrine; Rønning, Pål Andre & Niehusmann, Pitt [Show all 9 contributors for this article] (2025). Case report: Pseudoprogression mimicking neoplastic recurrence three months after completion of proton beam therapy for an IDH-mutant astrocytoma CNS WHO grade 3. doi: 10.3389/fonc.2025.1397912. Full text in Research Archive
• Heggebø, Liv Cathrine; Borgen, Ida Maria Henriksen; Rylander, Hillevi; Kiserud, Cecilie E.; Nordenmark, Tonje Kristin Haug & Hellebust, Taran Annette Paulsen [Show all 44 contributors for this article] (2023). Investigating survival, quality of life and cognition in PROton versus photon therapy for IDH- mutated diffuse grade 2 and 3 GLIOmas (PRO-GLIO): a randomised controlled trial in Norway and Sweden. BMJ Open. 13(3). doi: 10.1136/bmjopen-2022-070071. Full text in Research Archive Show summary

  Abstract Introduction The use of proton therapy increases globally despite a lack of randomised controlled trials demonstrating its efficacy and safety. Proton therapy enables sparing of non-neoplastic tissue from radiation. This is principally beneficial and holds promise of reduced long-term side effects. However, the sparing of seemingly non-cancerous tissue is not necessarily positive for isocitrate dehydrogenase (IDH)-mutated diffuse gliomas grade 2–3, which have a diffuse growth pattern. With their relatively good prognosis, yet incurable nature, therapy needs to be delicately balanced to achieve a maximal survival benefit combined with an optimised quality of life. Methods and analysis PRO-GLIO (PROton versus photon therapy in IDH-mutated diffuse grade 2 and 3 GLIOmas) is an open-label, multicentre, randomised phase III non-inferiority study. 224 patients aged 18–65 years with IDH-mutated diffuse gliomas grade 2–3 from Norway and Sweden will be randomised 1:1 to radiotherapy delivered with protons (experimental arm) or photons (standard arm). First intervention-free survival at 2 years is the primary endpoint. Key secondary endpoints are fatigue and cognitive impairment, both at 2 years. Additional secondary outcomes include several survival measures, health-related quality of life parameters and health economy endpoints. Ethics and dissemination To implement proton therapy as part of standard of care for patients with IDH-mutated diffuse gliomas grade 2–3, it should be deemed safe. With its randomised controlled design testing proton versus photon therapy, PRO-GLIO will provide important information for this patient population concerning safety, cognition, fatigue and other quality of life parameters. As proton therapy is considerably more costly than its photon counterpart, cost-effectiveness will also be evaluated. PRO-GLIO is approved by ethical committees in Norway (Regional Committee for Medical & Health Research Ethics) and Sweden (The Swedish Ethical Review Authority) and patient inclusion has commenced. Trial results will be published in international peer-reviewed journals, relevant conferences, national and international meetings and expert forums.

• Leske, Henning; Blakstad, Hanne Kristin; Lund-Iversen, Marius; Skovholt, Else K.; Niehusmann, Pitt & Ramm-Pettersen, Jon-Terje [Show all 11 contributors for this article] (2023). Astrocytoma (CNS WHO grade 4), IDH-mutant with co-occurrence of BRAF p.V600E mutation, and homozygous loss of CDKN2A. Neuropathology (Kyoto. 1993). ISSN 0919-6544. 43(5), p. 385–390. doi: 10.1111/neup.12895. Full text in Research Archive
• Schipmann, Stephanie; Sivakanesan, Sarankan; Rath, Daniel Stavne; Brandal, Petter; Vik-Mo, Einar Osland & Bjørås, Magnar [Show all 13 contributors for this article] (2023). Glioblastom hos voksne. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(2), p. 151–154. doi: 10.4045/tidsskr.22.0314. Full text in Research Archive Show summary

  lioblastom er den vanligste formen for primær hjernekreft hos voksne, og sykdommen har en alvorlig prognose. Selv om det er gjort store fremskritt i molekylær karakteristikk, har det ikke vært større gjennombrudd i behandlingen på mange år. Vi presenterer her en klinisk oversikt over dagens diagnostikk og behandling samt hvilke utfordringer og muligheter som ligger i å utvikle bedre og mer persontilpasset behandling.

• Husum, Yngvil Solheim; Skogen, Karoline; Brandal, Petter; Rønning, Pål Andre; Wigers, Andreas Reidar & Evang, Johan Arild [Show all 7 contributors for this article] (2022). Idiopathic Duro-Optic Calcification. Journal of neuro-ophthalmology. ISSN 1070-8022. 44(1). doi: 10.1097/WNO.0000000000001722. Full text in Research Archive
• Lysvik, Elisabeth Kirkeby; Fuster-Garcia, Elies; Revheim, Mona-Elisabeth; Svensson, Siri Fløgstad; Ager-Wick, Gunnhild & Bugge, Robin Antony Birkeland [Show all 12 contributors for this article] (2022). Multimodal imaging of vascular and molecular biomarkers in glioblastoma. Full text in Research Archive
• Blakstad, Hanne Kristin; Wohlleben, Christine; Saxhaug, Cathrine & Brandal, Petter (2022). SMART syndrome: two cases highlighting a complex and rare complication of brain irradiation. BMJ Case Reports. 15, p. 1–5. doi: 10.1136/bcr-2022-249599. Full text in Research Archive
• Toussaint, Laura; Brandal, Petter; Embring, Anna; Engellau, Jacob; Evensen, Morten Egeberg & Griskeviskius, Romualdas [Show all 30 contributors for this article] (2021). Inter-observer variation in target delineation and dose trade-off for radiotherapy of paediatric ependymoma. Acta Oncologica. ISSN 0284-186X. doi: 10.1080/0284186X.2021.2022202. Full text in Research Archive
• Bains, Simer Jit; Niehusmann, Pitt; Meling, Torstein Ragnar; Saxhaug, Cathrine; Züchner, Mark & Brandal, Petter (2019). Disseminated central nervous system hemangioblastoma in a patient with no clinical or genetic evidence of von Hippel-Lindau disease-a case report and literature review. Acta Neurochirurgica. ISSN 0001-6268. 161(2), p. 343–349. doi: 10.1007/s00701-019-03800-z. Full text in Research Archive
• Leske, Henning; Brandal, Petter; Rushing, Elisabeth J & Niehusmann, Pitt (2017). IDH-mutant giant cell glioblastoma: A neglected tumor variant? Clinical Neuropathology. ISSN 0722-5091. 36(6), p. 293–295. doi: 10.5414/NP301054. Full text in Research Archive
• Indelicato, Daniel J.; Merchant, Thomas; Laperriere, Normand; Lassen, Yasmin; Vennarini, Sabina & Wolden, Suzanne [Show all 23 contributors for this article] (2016). Consensus report from the Stockholm Pediatric Proton Therapy Conference. International Journal of Radiation Oncology, Biology, Physics. ISSN 0360-3016. 96(2), p. 387–392. doi: 10.1016/j.ijrobp.2016.06.2446. Full text in Research Archive
• Jeanmougin, M; Håvik, Annette Bentsen; Cekaite, Lina; Brandal, Petter; Sveen, Anders & Meling, Torstein Ragnar [Show all 11 contributors for this article] (2016). Primary and secondary glioblastomas: global expression analysis of two histologically indistinguishable tumor subtypes. Full text in Research Archive
• Varghese, Mercy; Nymoen, Hanne Marte Gjertsen; Saxhaug, Cathrine; Krossnes, Bård Kronen; Hosainey, Sayied Abdol Mohieb & Meling, Torstein Ragnar [Show all 7 contributors for this article] (2016). Symptomatic spinal metastasis from intracranial glioblastoma multiforme – Two illustrative cases and a review of the literature. Acta Oncologica. ISSN 0284-186X. 55(9-10), p. 1236–1253. doi: 10.3109/0284186X.2016.1161824. Full text in Research Archive
• Helseth, Eirik; Meling, Torstein Ragnar; Scheie, David; Wesenberg, Finn; Langmoen, Iver Arne & Brandal, Petter [Show all 7 contributors for this article] (2014). Intrakraniale svulster. In Gjerstad, Leif; Helseth, Eirik & Rootwelt, Terje (Ed.), Nevrologi og nevrokirurgi fra barn til voksen, 6. utg.. Forlaget Vett & Viten AS. ISSN 9788241207099. Full text in Research Archive
• Rogne, Siril Gudmundson; Helseth, Eirik; Brandal, Petter; Scheie, David & Meling, Torstein Ragnar (2014). Are melanomas averse to cerebellum? Cerebellar metastases in a surgical series. Full text in Research Archive
• Håvik, Annette Bentsen; Lind, Guro Elisabeth; Honne, Hilde; Meling, Torstein; Scheie, David & Hall, Kirsten Sundby [Show all 12 contributors for this article] (2014). Sequencing IDH1/2 glioma mutation hotspots in gliomas and malignant peripheral nerve sheath tumors. Neuro-Oncology. ISSN 1522-8517. 16(2), p. 320–322. doi: 10.1093/neuonc/not230. Full text in Research Archive

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