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  • 1
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    MGMT status through the ages, literally.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. e13550-e13550
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e13550-e13550
    Abstract: e13550 Background: It is known that in the setting of glioblastoma (GBM) having a methylated O6-Methylguanine Methyltransferase (MGMT) gene promoter confers a greater response to Temozolomide (TMZ) and an increased progression free survival (PFS) and overall survival (OS). Recent literature has uncovered interesting results when dichotomizing patients by demographics (i.e. age and gender) and analyzing response to the various available GBM therapies. Our primary objective is to analyze the effect of both age and MGMT status on OS and PFS in patients with newly diagnosed GBM. Understanding the role of MGMT on age in the setting of GBM can allow for a better understanding of disease course and treatment. Methods: 464 adult patients with newly diagnosed GBM and documented MGMT status were analyzed from a single major tertiary care institution between 2012 and 2018. Patients were stratified into four groups based on age (above or below 65 years) and MGMT status. A univariate Cox model was used to analyze the effect of age and MGMT status on PFS and OS, where our reference group was the group with the highest OS ( 〈 65/methylated). Results: The median age of the whole dataset was 63.4 years, and 65.2 years for patients who were MGMT methylated. Patients less than 65 years and were MGMT methylated had the best prognosis with a PFS and an OS of 10.9 months and 18.9 (Table), respectively. Patients above the age of 65 were more likely to be MGMT methylated (p = 0.002). There was an association between IDH1-mutant status and MGMT methylation (p = 0.006). Conclusions: Using MGMT status and age of the patient, our model predicts outcomes that can vary from 7.4 months to 18.9 months (HR = 3.41 p 〈 0.001).[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.e13550
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 2
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    Low platelet counts in patients with glioblastoma.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. e13565-e13565
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e13565-e13565
    Abstract: e13565 Background: Radiotherapy and concurrent chemotherapy with Temozolomide (TMZ) have myelosuppressive effect, and thrombocytopenia is commonly seen in this patient population seen in 5-10% of glioblastoma (GBM) patients. There is a lack of data analyzing the thrombocytopenia and it’s on the progression free survival (PFS) or overall survival (OS) of these patients. The primary objective of this study was to identify the degree of thrombocytopenia in newly diagnosed GBM patients receiving concurrent TMZ based chemoradiation (CRT). Secondary objectives included associations between thrombocytopenia PFS, and OS. Methods: We retrospectively reviewed 484 newly diagnosed GBM patients who underwent surgery followed by standard of care CRT. We also analyzed the association between platelet counts and age, sex, MGMT methylation status, and extent of surgical resection. Platelet count was collected at the time of surgery, CRT start date, and two, four, six, and ten weeks post-CRT start date. Patients were grouped into quartiles according to their platelets count. Results: Of the 484 patients collected, 308 were males, 139 had gross total resection of the tumor, 229 patients were older than 65 years, and 171 (42.1%) were MGMT methylated. In a univariate analysis, a platelet count less than 180,000 (lowest quartile) was associated with higher mortality (HR 1.63, P 〈 0.001) but had no significant association with PFS (HR 1.16, P = 0.48). Among the 118 patients who had platelet count lower than 180,000, 4 had platelets count less than 100,000 necessitating their TMZ to be stopped during CRT. In a multivariate analysis model adjusting for age, gender, MGMT status, and type of surgery, platelet counts less than 180,000 was also associated with significantly higher mortality (HR 1.60, P 〈 0.001). Conclusions: Our study concluded that patients who had platelet counts less than 180,000 at the time of surgery or CRT with TMZ had significantly higher mortality (HR 1.60, P 〈 0.001) but had no association with PFS (HR 1.16, P = 0.48).[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.e13565
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 3
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    EPID-33. GENDER-SPECIFIC PROBABILISTIC ATLASES OF GLIOBLASTOMA REVEAL IMPACT OF TUMOR LOCATION ON PROGRESSION FREE SURVIVAL
    Oxford University Press (OUP) ; 2019
    In:  Neuro-Oncology Vol. 21, No. Supplement_6 ( 2019-11-11), p. vi81-vi82
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 21, No. Supplement_6 ( 2019-11-11), p. vi81-vi82
    Abstract: Recent epidemiological studies suggest that gender differences in Glioblastoma (GBM) influence the prognostic outcome of patients, and thus should be considered for patient management. In this feasibility study, we developed population atlases of pre-treatment MRI lesions to evaluate whether progression free survival (PFS) in gender-specific GBM patients have a spatial proclivity to hemispheric or lobe-specific locations. METHODS 203 pre-operative MRI sequences (1.5T/3T T1w, T2w, FLAIR scans, multi-center) of GBM (125 males [m] & 78 females [f]) from TCIA (n=130), Ivy-GAP (n=32) and participating institution (n=41), along with PFS (median cut-off =189 days [m] , 78 days [f]) were analysed. Frequency atlases (improved PFS [i-PFS] & worse PFS [ω-PFS]) of tumor occurrence in T2/FLAIR hyperintense regions were developed for each gender, by averaging voxel intensities across all patients. To compute significant differences (p-value 〈 0.05), voxel-based analysis of differential involvement (ADIFFI) based on two-tailed Fisher’s exact test was performed on (a) m: i-PFS (n= 61) vs m: ω-PFS (n= 62), and (b) f: i-PFS (n= 39) vs f: ω-PFS (n= 39) atlases. Prominent clusters were identified and mapped to LONI Probabilistic Brain Atlas (LPBA40) parcellations to provide anatomic localization for each gender’s PFS. RESULTS ADIFFI analysis revealed that m: i-PFS tumors were more often localized to the inferior frontal gyrus of left hemisphere with a frequency of 20% whereas m: ω-PFS were more often localized to the right insular cortex (p 〈 0.005). f: i-PFS tumors were more often localized to the right hemisphere in the parietal and temporal lobe, while f: ω-PFS had 15.7% occurrence in the superior and middle frontal gyri of the right hemisphere (p 〈 0.03). CONCLUSION Our analysis suggests spatial proclivity of gender-specific PFS to hemispheric and lobe-specific locations in the brain. Gender-specific prognostic models and nomograms may be more accurate than unisex models and nomograms for GBM patients.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noz175.333
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 2094060-9
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  • 4
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    Foreign bodies of body orifices: A pictorial review
    Elsevier BV ; 2021
    In:  Clinical Imaging Vol. 80 ( 2021-12), p. 180-189
    Details
    In: Clinical Imaging, Elsevier BV, Vol. 80 ( 2021-12), p. 180-189
    Type of Medium: Online Resource
    ISSN: 0899-7071
    URL: Article
    DOI: 10.1016/j.clinimag.2021.07.006
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2004578-5
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  • 5
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    Albumin levels and Prognostic Nutritional Index in glioblastoma.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. e13567-e13567
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e13567-e13567
    Abstract: e13567 Background: Albumin levels are widely used to estimate patients’ nutritional status. Low perioperative albumin levels are associated with worse outcomes. Moreover, Prognostic Nutritional Index (PNI), which is calculated from serum albumin levels and peripheral blood lymphocyte count as follows: PNI = (Albumin x 10) + (0.005 x ALC), has been used to predict both short and long term outcomes in patients with wide variety of tumors. The primary objective of this study was to characterize perioperative albumin levels and PNI in newly diagnosed GBM patients. Secondary objectives included associations between albumin levels and PNI on progression free survival (PFS) and overall survival (OS). Methods: We retrospectively reviewed 568 newly diagnosed GBM patients who underwent surgery followed by standard of care chemoradiation. We analyzed the association between albumin and PNI on age, sex, MGMT methylation status, and extent of surgical resection on PFS and OS using a multivariate Cox proportional hazard model. Results: Of the 568 patients collected, 355 (62.5%) were males, 158 (27.8%) had gross total resection of the tumor, and 197(42.5%) were MGMT methylated. Both albumin and PNI were associated with OS but not PFS. The hazard ratio (HR) for OS among the top 2 quartiles of both albumin level and PNI were significantly higher than the bottom two quartiles. The median albumin level was 4.0 and the median PNI was 40. The point for significant high hazard ratio (HR) was around median value for both Albumin and PNI based on restricted cubic spine Cox regression models. The Kaplan-Meir (KM) estimated median OS was 15.2 months for albumin 〉 4, and 7.6 for albumin ≤4. The KM estimated median OS was 14.6 months for PNI 〉 40, and 5.7 for PNI≤40 (P logrank 〈 0.001 for both). While controlling for other factors that may also be associated with early death including age, gender, surgery type and MGMT status, HR = 1.9 (95% CI = 1.4- = 2.6) for Albumin 〈 4, and HR = 2.1 (95% CI = 1.5- 3.0) for PNI 〈 40 compared to their counterpart. Conclusions: Glioblastoma patients with perioperative albumin 〉 4 had a median OS of 15.2 months and 7.6 months for albumin ≤4, and a median OS of 14.6 months for PNI 〉 40 and 5.7 months for PNI≤40 (P logrank 〈 0.001 for both).
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.e13567
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 6
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    NIMG-75. RADIOMIC FEATURES LOCALIZED TO STEREOTACTIC BIOPSY LOCATIONS CAN CAPTURE EGFR PRESENCE IN GLIOBLASTOMA
    Oxford University Press (OUP) ; 2019
    In:  Neuro-Oncology Vol. 21, No. Supplement_6 ( 2019-11-11), p. vi178-vi178
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 21, No. Supplement_6 ( 2019-11-11), p. vi178-vi178
    Abstract: Epidermal growth factor receptor amplification (EGFRamp), occurs in 〉 60% of Glioblastoma (GBM) patients, and can predict response to alkylating chemotherapy. However, due to high genetic instability in GBM, a significant caveat to sampling EGFRamp during biopsy, is that reliable identification of its presence is dependent on the site of the biopsy, and may vary throughout the tumor. Previous studies have employed radiomics (computerized feature extraction) from the entire tumor to characterize EGFRamp presence. Our work is based on the rationale that radiomics measurements from stereotactic biopsy locations on Gd-T1w MRI, may allow to build accurate training models for predicting EGFRamp compared to using radiomic features from the entire tumor. METHODS MRI scans from 78 GBM subjects (33 EGFRamp, 45 non-amp) were obtained, of which 54 subjects were used for training while 24 were used for testing. Stereotactic biopsy locations were mapped by co-registering CT-images with MRIs (confirmed by two radiologists). For each biopsy region (1-cm diameter sphere), gradient entropy features and gender information were used to train a discriminant analysis classifier, on a voxel-wise manner. Our training model also included per-voxel spatial probabilities that were obtained by building atlases to quantify frequency of occurrence of EGFRamp and non-amp cases. All of these features were then used within the test set to predict EGFR status. RESULTS The model achieved a training accuracy of 81.4%, correctly classifying 17/23-amp, 27/31 non-amp cases. Accuracy on test set was 79.2% (7/10 amp, 12/14 non-amp cases correctly classified). Extracting features from the entire tumor achieved a training accuracy of 74% (17/23-amp, 23/31 non-amp cases correctly classified), and a testing accuracy of 70.8% (6/10 amp, 11/14 non-amp cases correctly classified). CONCLUSION Radiomic features, trained using features from only the stereotactic biopsy locations, may be more reliable in training models to predict EGFR mutation in GBM.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noz175.744
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
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  • 7
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    PATH-62. QUANTITATIVE ANALYSIS OF SEX-ASSOCIATED MGMT METHYLATION IN NEWLY DIAGNOSED GLIOBLASTOMA
    Oxford University Press (OUP) ; 2019
    In:  Neuro-Oncology Vol. 21, No. Supplement_6 ( 2019-11-11), p. vi157-vi157
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 21, No. Supplement_6 ( 2019-11-11), p. vi157-vi157
    Abstract: Glioblastoma (GBM) and MGMT have been reported to have sexual dimorphism. In multiple studies, including our own population-based cohort analysis, females had higher rates of MGMT methylation and improved methylation-associated progression-free and overall survival outcomes compared to males. MGMT methylation is assessed as a mean of five cysteine-phosphate-guanine (CpG1-5) islands (CpG methylation is highly inversely correlated with MGMT RNA expression). The primary objective of this study was to investigate differences in mean and individual CpG methylation by sex. METHODS 155 patients who underwent first surgical intervention for newly diagnosed GBM at a single tertiary care institution between 2016 and 2018 were reviewed. Of these, 135 patients had available CpG methylation data determined by a clinically validated test using bisulfate conversion followed by PCR and pyrosequencing. MGMT was defined as methylated if the mean of CpG1-5 ≥ 12. The mean of CpG1-5 and each CpG parameter were compared by sex using the Wilcoxon signed-rank test. RESULTS Overall (mean age 62, 34% female, 42% MGMT methylated), the median (IQR) of mean degree of methylation was 4.0% (2–33) and median CpG1-5 ranged from 3.0 to 4.5%. More females (53.3%) were MGMT methylated than males (37.1%). Females had significantly higher rates of mean methylation compared to males (14.0 vs 3.0%, p=0.046). Females also had higher rates of methylation at each CpG island compared to males CpG1(7.0 vs 3.0%, p=0.15), CpG2(8.0 vs 4.0%, p=0.10), CpG3(9.0 vs 4.0%, p=0.23), CpG4(7.0 vs 3.0%, p=0.047), and CpG5(6.0 vs 4.0%, p=0.097). CONCLUSION Females had higher rates of mean methylation and methylation of each CpG island compared to males, although only mean and CpG4 methylation values were statistically significant given the limited sample size. Further investigation with a larger cohort is ongoing to elucidate this dimorphism and establish whether sex-specific methylation cut-offs need to be implemented into clinical practice.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noz175.657
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
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  • 8
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    ATIM-40. CIRCULATING MYELOID-DERIVED SUPPRESSOR CELLS PREDICT FAVORABLE RESPONSE TO IMMUNE CHECKPOINT THERAPY IN A RANDOMIZED TRIAL OF NIVOLUMAB AND BEVACIZUMAB IN RECURRENT GBM
    Oxford University Press (OUP) ; 2019
    In:  Neuro-Oncology Vol. 21, No. Supplement_6 ( 2019-11-11), p. vi10-vi10
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 21, No. Supplement_6 ( 2019-11-11), p. vi10-vi10
    Abstract: Glioblastoma (GBM) creates an immunosuppressive environment that presents a challenge to efficacy of immunotherapeutic approaches. Results from the CheckMate-143 trial demonstrated responses in 8% of patients with nivolumab, underscoring the need for further insight into the mechanisms and markers of immune suppression and response. Given a limited set of biomarkers predictive of immunotherapy response in GBM, we explored the changes in immune cell populations in nivolumab and bevacizumab-treated GBM patients pre and post-treatment in order to help predict response. In these studies, we utilized traditional and newly developed approaches, including mass cytometry time-of-flight (CyTOF), single-cell RNA sequencing, and 10X Genomics simultaneous cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq). We analyzed patients’ samples in a randomized, phase 2 study of nivolumab and bevacizumab at GBM first recurrence (NCT03452579). Nine patients were identified as responders or non-responders at 8 weeks after therapy initiation. Utilizing peripheral blood samples, we observed a 6.4-fold decrease in immunosuppressive myeloid-derived suppressor cells (MDSCs) between baseline and first imaging follow-up in responders compared to non-responders, with a 4.9-fold decrease in the granulocytic MDSC (G-MDSC) subtype in responders over non-responders. While no significant changes in overall T-cell numbers were noted, expression of PD-1 on CD4+ T cells was significantly elevated at baseline and follow-up in responders as compared to non-responders – signatures which were confirmed by CyTOF. Given these immunophenotypic changes, preliminary results of a detailed investigation of this cohort by CITE-seq indicate that responders had increased IL7R-positive T cells post-treatment, which was not observed in non-responders. These results are currently being validated in an additional 40 patients that have been enrolled. Altogether, differences in immunophenotypes that were specific to responders and non-responders were observed, and characterization of these immune populations may be helpful in identifying GBM patients likely to benefit from immunotherapy.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noz175.039
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
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  • 9
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    PATH-13. SEX-LINKED TUMORAL MGMT STATUS AND OUTCOMES IN NEWLY DIAGNOSED GLIOBLASTOMA
    Oxford University Press (OUP) ; 2019
    In:  Neuro-Oncology Vol. 21, No. Supplement_6 ( 2019-11-11), p. vi145-vi145
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 21, No. Supplement_6 ( 2019-11-11), p. vi145-vi145
    Abstract: Glioblastoma (GBM) and MGMT have been reported to have sexual dimorphism. The primary objective of this study was to analyze the impact and association between sex and MGMT status on progression-free survival (PFS) and overall survival (OS) in patients with newly diagnosed GBM. METHODS 582 patients with newly diagnosed GBM who underwent first surgical intervention at a single tertiary care institution between 2012 and 2018 were reviewed. Adults with documented methylated (≥ 12) and un-methylated (≤ 7) MGMT status were included. A Kaplan-Meier and Cox proportional hazard models were used to analyze the association between sex and MGMT status on PFS and OS. RESULTS 464 adult patients (median age 63.4, 36.6% female) had documented MGMT status. Overall rate of MGMT methylated patients was 42.5%, while females were more often methylated than males (52.1% vs 37.4%, p=0.004). MGMT methylated compared to un-methylated females (median: 12.8 vs 7.4 months; 1-yr: 53% vs 27%) had a greater PFS benefit than males (median: 9.6 vs 6.8 months; 1-yr: 44% vs 23%). OS was significantly improved in MGMT methylated compared to un-methylated patients among females (p=0.001) but not among males (p=0.22). Among MGMT methylated patients, females had significantly better OS compared to males (median: 18.7 vs 12.4 months; 2-yr OS: 36.8% vs 24.3%, p=0.03). Although statistically not significant, a similar pattern was observed on PFS (median: 12.8 vs 9.6 months; 1-yr PFS: 52.6% vs 44.4%). Compared to MGMT methylated females, MGMT methylated males had a PFS HR=1.22 (95% CI=0.80 – 1.85, p=0.36), and an OS HR=1.45 (95% CI=1.03 – 2.04, p=0.032). CONCLUSION MGMT methylation is more common in females and methylation had a larger impact on both PFS and OS in females compared to males. These analyses highlight the need to further investigate sex differences that can inform clinical management of GBM.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noz175.609
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
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  • 10
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    Sexually dimorphic radiogenomic models identify distinct imaging and biological pathways that are prognostic of overall survival in glioblastoma
    Oxford University Press (OUP) ; 2021
    In:  Neuro-Oncology Vol. 23, No. 2 ( 2021-02-25), p. 251-263
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 23, No. 2 ( 2021-02-25), p. 251-263
    Abstract: Recent epidemiological studies have suggested that sexual dimorphism influences treatment response and prognostic outcome in glioblastoma (GBM). To this end, we sought to (i) identify distinct sex-specific radiomic phenotypes—from tumor subcompartments (peritumoral edema, enhancing tumor, and necrotic core) using pretreatment MRI scans—that are prognostic of overall survival (OS) in GBMs, and (ii) investigate radiogenomic associations of the MRI-based phenotypes with corresponding transcriptomic data, to identify the signaling pathways that drive sex-specific tumor biology and treatment response in GBM. Methods In a retrospective setting, 313 GBM patients (male = 196, female = 117) were curated from multiple institutions for radiomic analysis, where 130 were used for training and independently validated on a cohort of 183 patients. For the radiogenomic analysis, 147 GBM patients (male = 94, female = 53) were used, with 125 patients in training and 22 cases for independent validation. Results Cox regression models of radiomic features from gadolinium T1-weighted MRI allowed for developing more precise prognostic models, when trained separately on male and female cohorts. Our radiogenomic analysis revealed higher expression of Laws energy features that capture spots and ripple-like patterns (representative of increased heterogeneity) from the enhancing tumor region, as well as aggressive biological processes of cell adhesion and angiogenesis to be more enriched in the “high-risk” group of poor OS in the male population. In contrast, higher expressions of Laws energy features (which detect levels and edges) from the necrotic core with significant involvement of immune related signaling pathways was observed in the “low-risk” group of the female population. Conclusions Sexually dimorphic radiogenomic models could help risk-stratify GBM patients for personalized treatment decisions.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noaa231
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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