tbuckley/cabot-search huggingface dataset:
NIMG-36. PERFUSION, DIFFUSION, AND ANATOMICAL MRI BIOMARKERS FOR ASSESSING HISTOLOGICALLY-CONFIRMED MALIGNANT TRANSFORMATION IN MOLECULAR SUBTYPES OF IDH-MUTANT GLIOMAS
Authors: Nicholas Cho, Vien Le, Ashley Teraishi, Vicki Liu, Francesco Sanvito, Masanori Nakajo, Chencai Wang, Sonoko Oshima, Blaine Eldred, Jingwen Yao, Phioanh Nghiemphu, Noriko Salamon, Albert Lai, Timothy Cloughesy, Benjamin Ellingson
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Isocitrate dehydrogenase-mutant (IDHm) gliomas often initially present as low-grade (grade 2) gliomas but are expected to later progress into more aggressive higher-grade (grade 3-4) gliomas through malignant transformation (MT). MT is often determined non-invasively by emergence of contrast-enhancement on post-contrast T1-weighted magnetic resonance imaging (MRI), but contrast-enhancement is an imperfect surrogate for histologically-confirmed MT. This study explored perfusion, diffusion, and anatomical MRI biomarkers besides contrast-enhancement to study histologically-confirmed MT in IDHm 1p/19q-intact astrocytomas (IDHm-A) and IDHm 1p/19q-co-deleted oligodendrogliomas (IDHm-O). METHODS N=64 patients with initial histopathological grade 2 IDH-mutant glioma diagnosis who underwent repeated tissue sampling and were classified as histologically-confirmed MT (n=35) or non-MT (n=29) were retrospectively studied. Pre-surgical anatomical MRI (n=64) and, if available, diffusion-weighted imaging (n=61) and dynamic susceptibility contrast perfusion MRI (n=53) were analyzed. Tumor volumes of interest were segmented on the whole T2/FLAIR-hyperintense tumor. Measurable contrast enhancement (&amp;gt;1000mm3), tumor volume, sphericity, median apparent diffusion coefficient (ADC), and normalized relative cerebral blood volume (nrCBV) were compared between MT vs. non-MT IDHm-A and IDHm-O. RESULTS 81% of contrast-enhancing IDHm-A and 100% of contrast-enhancing IDHm-O underwent MT, while 41% of MT IDHm-A and 62% of MT IDHm-O were non-enhancing. Tumor volumes were significantly larger in the MT vs. non-MT groups for both IDHm-A (P=0.02) and IDHm-O (P=0.04). Whole tumor nrCBV was significantly higher (P=0.002), whole tumor ADC trended lower (P=0.06), and non-enhancing tumor sphericity was significantly lower (P=0.03) in MT vs. non-MT IDHm-A. There were no significant differences in ADC, nrCBV, nor sphericity when comparing MT vs. non-MT IDHm-O (P&amp;gt;0.05). CONCLUSIONS Many MT IDHm-gliomas remain non-enhancing. Tumor volumes can determine MT for both IDHm-A and IDHm-O. Diffusion and perfusion MRI show differences for MT in IDHm-A but not IDHm-O, which may reflect the different tumor biology of these IDHm molecular subtypes and their need for separate imaging biomarkers.
PATH-35. INTEGRATED GENOMIC ANALYSES OF IMMUNODEFICIENCY-ASSOCIATED EPSTEIN-BARR VIRUS- (EBV) POSITIVE PRIMARY CNS LYMPHOMAS
Authors: Leon D Kaulen, Evgeniya Denisova, Felix Hinz, Ling Hai, Dennis Friedel, Octavian Henegariu, Dirk C Hoffmann, Jakob Ito, Alexandros Kourtesakis, Pascal Lehnert, Sofia Doubrovinskaia, Philipp Karschnia, Louisa von Baumgarten, Tobias Kessler, Joachim M Baehring, Benedikt Brors, Felix Sahm, Wolfgang Wick
Journal: Neuro-Oncology (2024)

Abstract Immunodeficiency-associated primary CNS lymphoma (PCNSL) represents a distinct clinicopathological entity, which is typically Epstein-Barr virus positive (EBV+) and carries an inferior prognosis. Genetic alterations that characterize EBV related CNS lymphomagenesis remain unclear precluding molecular classification and targeted therapies. In this study, a comprehensive genetic analysis of 22 EBV+ PCNSL, integrated clinical and pathological information with exome and RNA sequencing (RNASeq) data. Deconvolution of bulk RNA sequencing data was performed using CIBERSORTx to characterize the tumor microenvironment. EBV+ PCNSL with germline controls carried a median of 55 protein-coding single nucleotide variants (SNVs; range 24-217) and 2 insertions/deletions (range 0-22). Genetic landscape was largely shaped by aberrant somatic hypermutation with a median of 41.01% (range 31.79-53.49%) of SNVs mapping to its target motifs. Tumors lacked established SNVs (MYD88, CD79B, PIM1) and copy number variants (CDKN2A, HLA loss) driving EBV negative PCNSL. Instead, EBV+ PCNSL were characterized by SOCS1 mutations (26%), predicted to disinhibit JAK/STAT signaling, and mutually exclusive gain-of-function NOTCH pathway SNVs (26%). Copy number gains were enriched on 11q23.3, a locus directly targeted for chromosomal aberrations by EBV, that includes SIK3 known to protect from cytotoxic T-cell responses. Losses covered 5q31.2 (STING), critical for sensing viral DNA, and 17q11 (NF1). Unsupervised clustering of RNASeq data revealed two distinct transcriptional groups, that shared strong expression of CD70 and IL1R2, previously linked to tolerogenic tumor microenvironments. Correspondingly, deconvolution of bulk RNASeq data revealed elevated M2-macrophage, T-regulatory cell, mast cell and monocyte fractions in EBV+ PCNSL. In addition to novel insights into the pathobiology of EBV+ PCNSL, the data provide the rationale for the exploration of targeted therapies including JAK-, NOTCH- and CD70-directed approaches.
PATH-34. IT NEVER RAINS BUT IT POURS - DIAGNOSING ANAPLASTIC PLEOMORPHIC XANTHASTROCYTOMA TWICE IN A FORTNIGHT - OUR EXPERIENCE IN A RESOURCE CONSTRAINED SETTING
Authors: Durgapoorna Menon, Supriya Menon, Vigneswar SB, Vani Santosh, Kiron G, Dilip Panikar, Shyamsundar S
Journal: Neuro-Oncology (2024)

Abstract Grade 3 Pleomorphic Xanthastrocytoma is a rare tumour (less than 1% of all astrocytic glial neoplasms). Present most commonly with seizures. Surgery and Radiation remain the mainstay of treatment with no clear role for traditional systemic chemotherapies; BRAF inhibitors show some benefit. We report two cases who were diagnosed within a month of each other - one was initially diagnosed in 2017- presented with altered smell, headache and diplopia. Found to have a well-defined lobulated heterogeneously enhancing suprasellar parasellar lesion. After Gross Total Resection, was diagnosed from various centers as Anaplastic Ependymoma WHO Grade III; Gllioblastoma WHO Grade IV; Anaplastic Pleomorphic Xanthastrocytoma WHO Grade III. Based on immunohistochemistry, was considered Anaplastic Ependymoma WHO Grade III. Spine screening was negative; received adjuvant Radiation 60Gy in 30 fractions. After a disease free interval of 6 years, developed a recurrence at the post op site. He underwent repeat decompression and the histopathology showed Grade 3 Pleomorphic Xanthastrocytoma. Immunohistochemistry- OLIG2: diffuse positive; R132H p.IDH1: negative; ATRX: intact nuclear expression; Mismatch repair proteins (MSH2, MSH6, MLH1, PMS2); intact nuclear expression; MIB-1 labelling index: 10-12%; H3 p.K27M: negative; GFAP: variable positivity; Podoplanin and p53 shows focal positivity; EMA, CD 34 are negative. He competed Reirradiation in January 2024. He is asymptomatic and on follow up. The second case -15 year old boy presented with episodes of absence seizures. Imaging showed a predominantly extraaxial lesion at tentorial apex. He underwent decompression and histopathology showed Grade 3 Pleomorphic Xanthastrocytoma. Immunohistochemistry - cells positive for S100 and variably positive for GFAP, OLIG2 and vimentin; ATRX: Retained expression, IDH1p.R132H, EMA, Synaptophysin, Neu N: Negative, p53: Focally positive, CD34: Positive in few tumour cells, Ki-67: 14-16 %.V600 mutation detected in the BRAF gene. Had Adjuvant RT 60 Gy in 30 fractions -completed in March 2024. MRI at 1 month - no significant change in overall tumour burden compared to post operative MRI. Was offered Dabrafenib with Trametinib.
BIOS-03. CLINICAL PRESENTATION, MANAGEMENT, AND OUTCOME IN NEUROLYMPHOMATOSIS: A SYSTEMATIC REVIEW AND ANALYSIS OF INDIVIDUAL PATIENT DATA FROM 459 CASES
Authors: Leon D Kaulen, Thomas Hielscher, Sofia Doubrovinskaia, Dirk C Hoffmann, Tobias Kessler, Benjamin-Leon Traub, Joachim Baehring, Wolfgang Wick
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Neurolymphomatosis (NL) refers to lymphomatous infiltration of the peripheral nervous system (PNS). NL diagnosis and treatment are challenging given the broad differential diagnosis of peripheral neuropathy, the lack of larger cohorts and the subsequent unavailability of prognostic factors or consensus therapy. This study aimed to define characteristics and prognostic factors of NL. METHODS A systematic review of the literature (2004-2023) was performed using PubMed and Scopus databases and reported following PRISMA guidelines. Clinical, radiological, pathological and outcome information were extracted. Multivariable survival analyses were performed using Cox proportional hazard models. RESULTS A total of 459 NL cases from 264 studies were accumulated. NL was the first manifestation of malignancy (primary NL) in 197 patients. PNS relapse of known non-Hodgkin lymphoma (secondary NL) occurred in 262 cases after a median 12 months. NL predominantly presented with rapidly deteriorating, asymmetric painful polyneuropathy. Infiltrated structures included peripheral nerves (56%), nerve roots (52%), plexus (33%) and cranial nerves (32%). Diagnosis was established at a median of 3 months after symptom onset with substantial delays in primary NL. It mainly relied on PNS biopsy or FDG-PET, which carried high diagnostic yields (&amp;gt; 90%). Post mortem diagnoses were rare (3%). Most cases were classified as B-cell (90%) lymphomas. Tumor-directed therapy was administered in 96% of patients and typically consisted of methotrexate or rituximab-based polychemotherapy. Median overall survival was 18 months. Primary NL without concurrent systemic disease outside the nervous system (hazard ratio [HR]: 0.44; 95% confidence interval (CI): 0.25-0.78; p = 0.005), performance status (ECOG &amp;lt; 2, HR: 0.30; 95% CI: 0.18-0.52; p &amp;lt; 0.0001), and rituximab-based treatment (HR: 0.46; 95% CI: 0.28-0.73; p = 0.001) were identified as favorable prognostic markers on multivariable analysis when adjusting for clinical and sociodemographic parameters. CONCLUSIONS Advances in neuroimaging modalities, particularly FDG-PET, facilitate NL diagnosis and offer a high diagnostic yield. Rituximab-based therapy improves NL outcome. Findings may assist clinicians in early recognition, prognostic stratification, and treatment of NL.
EXTH-30. GENETIC ALTERATIONS THAT DEREGULATE RB AND PDGFRA SIGNALING PATHWAYS DRIVE TUMOR PROGRESSION IN IDH2-MUTANT ASTROCYTOMA
Authors: Kensuke Tateishi, Yohei Miyake, Taishi Nakamura, Satoshi Fujii, Tetsuya Yamamoto, Daniel Cahill, Hiroaki Wakimoto
Journal: Neuro-Oncology (2024)

Abstract In IDH-mutant astrocytoma, IDH2 mutation is quite rare and biological mechanisms underlying tumor progression in IDH2-mutant astrocytoma remain unclear. In this presentation, we report a unique case of IDH2 mutant astrocytoma, CNS WHO grade 3 that developed tumor progression. We performed a comprehensive genomic and epigenomic analysis for primary and recurrent tumors and found that both tumors harbored recurrent IDH2R172K and TP53R248W mutation with CDKN2A/B hemizygous deletion. We also found amplifications of CDK4 and MDM2 with PDGFRA gain in the recur- rent tumor and upregulated protein expressions of these genes. We further developed, for the first time, a xenograft mouse model of IDH2R172K and TP53R248W mutant astrocytoma from the recurrent tumor, but not from the primary tumor. Consistent with parent recurrent tumor cells, amplifications of CDK4 and MDM2 and PDGFRA gain were found, while CDKN2A/B was identified as homozygous deletion in the xenografts, qualifying for integrated diagnosis of astro- cytoma, IDH2-mutant, CNS WHO grade 4. Cell viability assay found that CDK4/6 inhibitor and PDGFR inhibitor potently decreased cell viability in recurrent tumor cells, as compared to primary tumor cells. On the other hand, in accord with our previous study that IDH1 inhibitor was not sufficient to induce anti-tumor effects in IDH1-mutant high-grade gliomas (Tateishi K et al. Cancer Cell. 2015), we did not find decreased cell viability nor histone methylation status changes after mutation specific IDH2 inhibitor treatment of recurrent cells. These findings underlie that gene alterations that activate retinoblastoma (RB) signaling pathways and PDGFR may drive tumor progression and xenograft formation in IDH2-mutant astrocytoma, which is equivalent to progressive IDH1-mutant astrocytoma. Also, our findings suggest that these genomic alterations may represent therapeutic targets in IDH2-mutant astrocytoma.
EPID-20. PRIMARY INTRAMEDULLARY PILOMYXOID ASTROCYTOMA OF SPINAL CORD (PIPASC): A SYSTEMATIC REVIEW OF CASE REPORTS AND CASE SERIES OF TWO DECADES
Authors: Haseeb Mehmood Qadri, Asif Bashir
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Pilomyxoid Astrocytoma (PMA), new variant of pilocytic astrocytoma, is more aggressive and relatively rare, mostly seen in children and commonly found in brain. Primary intramedullary pilomyxoid astrocytoma of spinal cord (PIPASC) is extremely rare. The distinct aggressive and pathological behavior, poor prognosis and the diversity in response to various treatment modalities makes the PIPASC an oncologic enigma. We aim to evaluate the clinical manifestations, histopathologic spectrum and onco-surgical management of this neoplasm. MATERIALS AND METHODS After an extensive literature search using PubMed Central and Google Scholar, eight case reports and one case series of patients with spinal PA were retrieved and included using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines without applying any filter of time, study type or place. Case presentations of 12 patients were analyzed in this review. RESULTS Pediatric preponderance of the neoplasm (75%) with the mean age of 7.90 ± 4.51 years was noted. Sensory deficits and scoliotic deformity were the most common presenting symptom and sign in 83.33% and 33.33% of patients, respectively. Thoracic spine (50%) was most commonly affected region. MRI showed the most consistent findings of cord compression in 100% cases and the lesion appeared hypointense on T1- weighted images (T1WI) and hyperintense on T2-weighted images (33.33%). The average post treatment survival duration was found to be more than 2 years. CONCLUSIONS Occurrence of PIPASC among pediatric population is rare. They have possibility of extraneural metastasis, can differentiate into more malignant glioma and get recurrent due to which they require a long-term follow-up of the patients. Further studies are required to investigate the utility of chemotherapy and radiotherapy in its management.
PATH-26. MIDLINE INVOLVEMENT IS ASSOCIATED WITH ABERRANT RB1 SIGNALING IN PATIENTS WITH GRADE 4 IDH-MUTANT ASTROCYTOMA
Authors: Muhammad Asad Maqbool, Robert B Jenkins, Cristiane M Ida, Terence C Burns, Sani H Kizilbash
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND The prognostic factors impacting the survival of grade 4 IDH-mutant astrocytoma treated with standard radiation/temozolomide are not well-described. METHODS A retrospective cohort was generated of all patients diagnosed at Mayo Clinic with grade 4 IDH-mutant astrocytoma (2021 WHO Classification) on initial diagnosis between 2002-2023, and who received standard radiation/temozolomide. The impact of patient, tumor and molecular variables on overall survival (OS) and progression-free survival (PFS) was evaluated using survival analyses and Cox regression models. RESULTS Fifty-eight patients were identified. The median age was 36 years, 64% were male and 93% were white. The median follow up was 3.3 years. The median OS and PFS were 6.9 years and 2.4 years, respectively. CDKN2A/B homozygous deletion significantly reduced both OS (2.5 years vs NR, HR=3.9, p=0.0168) and PFS (1.4 vs 4.5 years, HR=4.2, p=0.0005). Midline involvement (brainstem, basal ganglia, thalamus, cerebellum or corpus callosum) also significantly reduced both OS (2.4 vs 12.8 years, HR=7.0, p=0.0014) and PFS (1.4 vs 4.5 years, HR=4.8, p=0.0002). MGMT promoter hypermethylation showed a trend toward significance for PFS (p=0.082) but did not impact OS. Age, sex, tumor size, ATRX immunohistochemistry and tumor-treating field therapy did not impact survival outcomes. Multivariable analyses revealed that PFS remained significantly impacted by both CDKN2A/B homozygous deletion (HR=3.5, p=0.0051) and midline involvement (HR=3.1, p=0.0125). A significant association between CDKN2A/B homozygous deletion and midline involvement was unexpectedly observed (53% if midline, 24% if non-midline; χ2=4.3, p=0.037). Exploratory analyses revealed that 15/15 (100%) of patients with midline involvement demonstrated aberration in RB1 signaling (CDKN2A/B homozygous deletion, n=8; CDKN2A/B hemizygous deletion or loss of heterozygosity, n=6; CDK4 amplification, n=1). CONCLUSION CDKN2A/B homozygous deletion and midline involvement independently impact PFS in patients with grade 4 IDH-mutant astrocytoma treated with standard radiation/temozolomide. Furthermore, midline involvement may be associated with aberrant RB1 signaling.
BIOM-39. GENOMIC AND CLINICAL ASSOCIATIONS WITH RADIATION NECROSIS IN PATIENTS WITH DIFFUSE INFILTRATING GLIOMAS
Authors: Michael Kienhöfer, Heather Lin, Erick Campbell, Chetna Wathoo, Surya Bhat, Subha Perni, Vinay Puduvalli, Nazanin K Majd
Journal: Neuro-Oncology (2024)

Abstract BACKGROUND Radiation necrosis (RN) is a complication of radiotherapy (RT) that can significantly affect quality of life and outcomes in patients with gliomas. Clinical and molecular factors predisposing patients to RN are not clearly established. We hypothesize that clinicogenomic data can be leveraged to identify patients at high risk for RN. METHODS We identified patients from 2014-2024 with diffuse gliomas and RN diagnosed based on Advanced-Brain-Tumor-Imaging which includes conventional MRI, 3 perfusion parameters, spectroscopy and/or pathology at MD Anderson. Inclusion criteria included diagnosis of RN 12-weeks after RT and concordance of 4 ABTI parameters. For each case, we identified 2 controls who were gender-,diagnosis-, and age-matched using a nearest neighborhood algorithm. We evaluated the correlation between 15 most mutated genes in baseline tissue and occurance of RN. A logistic regression model was employed to assess the multivariable relationship between patient characteristics, gene mutations, and RN. RESULTS We identified 62 patients with RN; 50 glioblastoma (80.6%), 8 diffuse astrocytoma (12.9%) and 4 oligodendroglioma (6.5%). Time from RT to RN diagnosis was 254 days (IQR 154-483). 18(29%) of RN cases and 29(24.4%) of controls had received more than one course of RT. Patients treated with bevacizumab before RT had significantly lower odds of developing RN compared to those who did not receive bevacizumab (OR 0.103 [0.011 – 0.960], p=0.0459). BRAF mutations were more frequent in the RN cohort (8.1% vs. 2.4%) and patients with BRAF mutation were more likely to have RN than those without BRAF mutation (OR 6.842 [1.2, 39.01], p=0.0304). Age, gender, diagnosis, IDH, MGMT or 1p19q status were not associated with RN. CONCLUSION We found that bevacizumab administration was associated with a significant reduction in RN development. We also found a novel association between presence of BRAF mutations and increased risk of RN in glioma patients, which warrants further investigation.
NIMG-31. CASE REPORT: DIAGNOSIS OF AN INFILTRATIVE GLIOMA IN A LI-FRAUMENI SYNDROME PATIENT OBSCURED BY LESION RESPONSIVENESS TO NSCLC TREATMENT
Authors: Zachary Janatpour, Timothy Gregory
Journal: Neuro-Oncology (2024)

Abstract Li-Fraumeni syndrome is a rare, autosomal dominant disorder linked to germline mutations of the TP53 suppressor gene. Patients with this syndrome are predisposed to various malignancies and a variety of brain tumors to include choroid plexus carcinoma, medulloblastoma, and glioma. We present a 46-year-old woman with a history of Li-Fraumeni syndrome which manifested with multiple systemic malignancies including breast cancer, ovarian teratoma, and leiomyosarcoma. The patient had been undergoing MRI brain surveillance since 2018, which was initially notable for a right cerebellar midline focus of enhancement associated with slowly evolving right middle cerebellar peduncle FLAIR signal, with no detectable neurologic symptoms. She underwent systemic therapy for non-small cell lung cancer (NSCLC) with pemetrexed/cisplatin. Her next MRI brain in August 2023 showed resolution of the cerebellar enhancement with small residual FLAIR signal. In April 2024, the patient presented with new neurologic symptoms to include ataxia, dizziness, difficulty swallowing, and memory loss. Repeat MRI brain revealed new infiltrative FLAIR signal throughout the right temporal lobe extending from the posterior fossa, contiguous with the previously seen cerebellar findings and consistent with infiltrative glioma. Due to fragmented records and care in multiple systems, her updated MRI initially created a diagnostic challenge with a radiographic interpretation of likely encephalitis. This is a unique case documenting a middle-aged female with Li-Fraumeni syndrome, followed for multiple cancers, presenting with new neurologic symptoms and progressive infiltrative FLAIR changes spanning from the cerebellum into the right temporal lobe. These findings highlight the natural history of a TP53 deficient tumor that ostensibly responded to a cisplatin-based regimen given for a different indication, thereby delaying time to symptom onset and need for biopsy. Surveillance of low grade lesions in patients with underlying tumor predisposition syndromes must be interpreted in context of systemic disease burden and concurrent treatments for other neoplasms.
PATH-27. MOLECULAR, IMAGING, AND SURVIVAL MANIFESTATIONS IN MOLECULAR GLIOBLASTOMAS: INSIGHTS FROM A MULTI-NATIONAL STUDY
Authors: Yae Won Park, Gilbert Youssef, Nicolas Freeman, Nico Teske, Philipp Karschnia, Martha Foltyn-Dumitru, Rouzbeh Banan, Matthew Lee, Kanwar Singh, Ji Eun Park, Kyu Sung Choi, Doonyaporn Wongsawaeng, Jong Hee Chang, Se Hoon Kim, Seung-Koo Lee, Patrick Y Wen, Ramon Francisco Barajas Jr, Seung Hong Choi, Ho Sung Kim, Rajan Jain, Felix Sahm, Wolfgang Wick, Martin Bendszus, Philipp Vollmuth, Niklas Thon, Raymond Huang, Sung Soo Ahn
Journal: Neuro-Oncology (2024)

Abstract Apart from the traditional definition of IDH-wildtype GBM based on histological characteristics, IDH-wildtype diffuse gliomas previously assigned to histological grade 2 or 3 are now defined as IDH-wildtype GBM in the presence of qualifying molecular markers (TERTp mutation, EGFR amplification, or chromosome +7/-10) (“molecular GBM”) in the 2021 WHO classification. However, the clinical significance of molecular GBM is unrevealed. This collaboration aims to comprehensively evaluate the clinical, molecular, imaging characteristics, and prognosis of molecular GBMs in a multi-national dataset and stratify survival. Retrospective chart and imaging review was performed in 258 molecular GBM patients from eight centers across three continents. Clinical, molecular, imaging, and survival characteristics were analyzed. The median age of molecular GBM patients was 58 years (range: 23-83) with 139 males, with TERTp mutation (83 of 214 [38.8%]), EGFR amplification (160 of 204 [78.4%]), and chromosome +7/-10 (82 of 143 patients [57.3%]). The majority of tumors were located at the frontal and temporal lobes (48.4%) and exhibited non-contrast-enhancing (CE) tumors (73.7%). Gliomatosis cerebri pattern was shown with 27 patients (12.4%). The median OS was 28.1 months (95% confidence interval 22.1-34.1). There was significantly shorter survival in patients with high Ki-67 index (&amp;gt; 20) compared to those with low Ki-67 index (median OS 19.3 vs. 31.5 months, log-rank test P = 0.002), while no survival differences were found according to histological grade or molecular diagnostics. Survival was significantly shorter in patients with infiltrative imaging appearance compared to those without (median OS 24.7 vs 41.0 months, log-rank test P = 0.014). In conclusion, survival within molecular GBM patients may be heterogeneous and associated with Ki-67 index and infiltrative imaging appearance.