scholarly journals Functional Diffusion Map As an Early Imaging Biomarker for High-Grade Glioma: Correlation With Conventional Radiologic Response and Overall Survival

2008 ◽  
Vol 26 (20) ◽  
pp. 3387-3394 ◽  
Author(s):  
Daniel A. Hamstra ◽  
Craig J. Galbán ◽  
Charles R. Meyer ◽  
Timothy D. Johnson ◽  
Pia C. Sundgren ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Survival ◽  
Patient Survival ◽  
Characteristic Curve ◽  
High Grade Glioma ◽  
Cox Proportional Hazards ◽  
Response To Therapy ◽  
Imaging Biomarker ◽  
High Grade ◽  
Diffusion Map

PurposeAssessment of radiologic response (RR) for brain tumors utilizes the Macdonald criteria 8 to 10 weeks from the start of treatment. Diffusion magnetic resonance imaging (MRI) using a functional diffusion map (fDM) may provide an earlier measure to predict patient survival.Patients and MethodsSixty patients with high-grade glioma were enrolled onto a study of intratreatment MRI at 1, 3, and 10 weeks. Receiver operating characteristic curve analysis was used to evaluate imaging parameters as a function of patient survival at 1 year. Both log-rank and Cox proportional hazards models were utilized to assess overall survival.ResultsGreater increases in diffusion in response to therapy over time were observed in those patients alive at 1 year compared with those who died as a result of disease. The volume of tumor with increased diffusion by fDM at 3 weeks was the strongest predictor of patient survival at 1 year, with larger fDM predicting longer median survival (52.6 v 10.9 months; log-rank, P < .003; hazard ratio [HR] = 2.7; 95% CI, 1.5 to 5.9). Radiologic response at 10 weeks had similar prognostic value (median survival, 31.6 v 10.9 months; log-rank P < .0007; HR = 2.9; 95% CI, 1.7 to 7.2). Radiologic response and fDM differed in 25% of cases. A composite index of response including fDM and RR provided a robust predictor of patient survival and may identify patients in whom RR does not correlate with clinical outcome.ConclusionCompared with conventional neuroimaging, fDM provided an earlier assessment of equal predictive value, and the combination of fDM and RR provided a more accurate prediction of patient survival than either metric alone.

EPID-06. ASSOCIATIONS BETWEEN GERMLINE GENETIC VARIANTS AND OVERALL SURVIVAL IN PATIENTS WITH GLIOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi86-vi86
Author(s):  
Kunal Potnis ◽  
Quinn Ostrom ◽  
Elizabeth Claus
Keyword(s):  
Overall Survival ◽  
Genetic Variation ◽  
Genetic Variants ◽  
Cancer Susceptibility ◽  
High Grade Glioma ◽  
Cox Proportional Hazards ◽  
Small Sample ◽  
Hazard Ratio ◽  
Low Grade ◽  
High Grade

Abstract BACKGROUND In addition to somatic genetic variation in tumors, germline genetic variation can better define cancer susceptibility risk, guide therapy, and predict survival. Most prior research into associations between germline genetic variants and survival outcomes in patients with glioma has been limited by small sample sizes and to high-grade glioma only. This study is the first to use data from Brigham and Women’s Hospital (BWH) and to include both low-grade and high-grade glioma cases to explore associations between germline genetic variants and overall survival. METHODS This study included 211 patients enrolled at BWH from April 2010 to January 2020. Ninety-two candidate germline genetic variants were identified via literature review. Fifty-five variants with minor allele frequency &gt;0.05 were included preliminarily, for which bivariate Cox proportional hazards regression models were employed. Twenty-two variants with P&lt; 0.5 were included in the final multivariable model, adjusted for patient sex, age, race, and glioma grade. Stratified sub-analyses were also conducted by sex. Associations were considered statistically significant at P&lt; 0.05. RESULTS Among all patients, homozygous C/C genotype at rs17655 (ERCC5 gene) was significantly associated with worse overall survival (hazard ratio=2.61, P=0.0095). Among females only, worse survival was associated with homozygous T/T genotype at rs1381057 (POLQ, hazard ratio=2.58, P=0.046). Among males only, heterozygous status for the A genotype at rs487848 (POLQ, hazard ratio=0.31, P=0.018) and the A genotype at rs1468923 variant (PIK3CA, hazard ratio=0.51, P=0.016) were associated with improved survival. CONCLUSION We identified statistically significant associations between overall survival and four variants in genes involved in DNA repair and the PIK3 pathway, three of which were sex-specific. Our results contribute to improving patient stratification in glioma and may lead to increased targeting of treatment strategies.

scholarly journals Evaluation of the functional diffusion map as an early biomarker of time-to-progression and overall survival in high-grade glioma

2005 ◽  
Vol 102 (46) ◽  
pp. 16759-16764 ◽  
Author(s):  
D. A. Hamstra ◽  
T. L. Chenevert ◽  
B. A. Moffat ◽  
T. D. Johnson ◽  
C. R. Meyer ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Grade Glioma ◽  
High Grade ◽  
Time To Progression ◽  
Diffusion Map ◽  
Early Biomarker

Sex, Age, Anatomic Location, and Extent of Resection Influence Outcomes in Children With High-grade Glioma

Neurosurgery ◽  
2015 ◽  
Vol 77 (3) ◽  
pp. 443-453 ◽  
Author(s):  
Heather J. McCrea ◽  
Evan D. Bander ◽  
Rachael A. Venn ◽  
Anne S. Reiner ◽  
J. Bryan Iorgulescu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pediatric Population ◽  
High Grade Glioma ◽  
Extent Of Resection ◽  
Cox Proportional Hazards ◽  
Survival Duration ◽  
Subtotal Resection ◽  
High Grade ◽  
Female Patients ◽  
Male Patients

Abstract BACKGROUND: Survival duration and prognostic factors in adult high-grade glioma have been comprehensively analyzed, but less is known about factors contributing to overall survival (OS) and progression-free survival (PFS) in pediatric patients. OBJECTIVE: To identify these factors in the pediatric population. METHODS: We retrospectively reviewed institutional databases evaluating all patients ⩽21 years with high-grade glioma treated between 1988 and 2010. Kaplan-Meier curves and log-rank statistics were used to compare groups univariately. Multivariate analyses were completed using Cox proportional hazards regression models. RESULTS: Ninety-seven patients were identified with a median age of 11 years. Median OS was 1.7 years, and median PFS was 272 days. Location was significant for OS (P &gt; .001). Patients with gross total resection (GTR) had a median OS of 3.4 years vs 1.6 years for subtotal resection and 1.3 years for biopsy patients (P &gt; .001). Female patients had improved OS (P = .01). Female patients with GTR had a mean OS of 8.1 years vs 2.4 years for male patients with GTR and 1.4 years for all other female patients and male patients (P = .001). PFS favored patients ⩽3 and ≥13 years and females (P = .003 and .001). CONCLUSION: OS was significantly correlated with the location of the tumor and the extent of resection. GTR significantly improved overall survival for both glioblastoma multiforme and anaplastic astrocytoma patients, and female patients showed a much larger survival benefit from GTR than male patients.

Proliferation-dominant high-grade astrocytoma: survival benefit associated with extensive resection of FLAIR abnormality region

2020 ◽  
Vol 132 (4) ◽  
pp. 998-1005 ◽  
Author(s):  
Haihui Jiang ◽  
Yong Cui ◽  
Xiang Liu ◽  
Xiaohui Ren ◽  
Mingxiao Li ◽  
...  
Keyword(s):  
Survival Benefit ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Characteristic Curve ◽  
Extent Of Resection ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
High Grade ◽  
Extensive Resection ◽  
High Grade Astrocytoma

OBJECTIVEThe aim of this study was to investigate the relationship between extent of resection (EOR) and survival in terms of clinical, molecular, and radiological factors in high-grade astrocytoma (HGA).METHODSClinical and radiological data from 585 cases of molecularly defined HGA were reviewed. In each case, the EOR was evaluated twice: once according to contrast-enhanced T1-weighted images (CE-T1WI) and once according to fluid attenuated inversion recovery (FLAIR) images. The ratio of the volume of the region of abnormality in CE-T1WI to that in FLAIR images (VFLAIR/VCE-T1WI) was calculated and a receiver operating characteristic curve was used to determine the optimal cutoff value for that ratio. Univariate and multivariate analyses were performed to identify the prognostic value of each factor.RESULTSBoth the EOR evaluated from CE-T1WI and the EOR evaluated from FLAIR could divide the whole cohort into 4 subgroups with different survival outcomes (p < 0.001). Cases were stratified into 2 subtypes based on VFLAIR/VCE-T1WIwith a cutoff of 10: a proliferation-dominant subtype and a diffusion-dominant subtype. Kaplan-Meier analysis showed a significant survival advantage for the proliferation-dominant subtype (p < 0.0001). The prognostic implication has been further confirmed in the Cox proportional hazards model (HR 1.105, 95% CI 1.078–1.134, p < 0.0001). The survival of patients with proliferation-dominant HGA was significantly prolonged in association with extensive resection of the FLAIR abnormality region beyond contrast-enhancing tumor (p = 0.03), while no survival benefit was observed in association with the extensive resection in the diffusion-dominant subtype (p=0.86).CONCLUSIONSVFLAIR/VCE-T1WIis an important classifier that could divide the HGA into 2 subtypes with distinct invasive features. Patients with proliferation-dominant HGA can benefit from extensive resection of the FLAIR abnormality region, which provides the theoretical basis for a personalized resection strategy.

scholarly journals How well do neurosurgeons predict survival in patients with high-grade glioma?

2021 ◽  
Author(s):  
Lisa Millgård Sagberg ◽  
Asgeir S. Jakola ◽  
Ingerid Reinertsen ◽  
Ole Solheim
Keyword(s):  
Median Survival ◽  
Survival Curve ◽  
Binary Logistic Regression ◽  
High Grade Glioma ◽  
Accurate Estimation ◽  
Binary Logistic Regression Analysis ◽  
High Grade ◽  
Clinical Prediction ◽  
Individual Level ◽  
Actual Survival

AbstractDue to the lack of reliable prognostic tools, prognostication and surgical decisions largely rely on the neurosurgeons’ clinical prediction skills. The aim of this study was to assess the accuracy of neurosurgeons’ prediction of survival in patients with high-grade glioma and explore factors possibly associated with accurate predictions. In a prospective single-center study, 199 patients who underwent surgery for high-grade glioma were included. After surgery, the operating surgeon predicted the patient’s survival using an ordinal prediction scale. A survival curve was used to visualize actual survival in groups based on this scale, and the accuracy of clinical prediction was assessed by comparing predicted and actual survival. To investigate factors possibly associated with accurate estimation, a binary logistic regression analysis was performed. The surgeons were able to differentiate between patients with different lengths of survival, and median survival fell within the predicted range in all groups with predicted survival < 24 months. In the group with predicted survival > 24 months, median survival was shorter than predicted. The overall accuracy of surgeons’ survival estimates was 41%, and over- and underestimations were done in 34% and 26%, respectively. Consultants were 3.4 times more likely to accurately predict survival compared to residents (p = 0.006). Our findings demonstrate that although especially experienced neurosurgeons have rather good predictive abilities when estimating survival in patients with high-grade glioma on the group level, they often miss on the individual level. Future prognostic tools should aim to beat the presented clinical prediction skills.

scholarly journals Determining optimal clinical target volume margins in high-grade glioma based on microscopic tumor extension and magnetic resonance imaging

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Shulun Nie ◽  
Yufang Zhu ◽  
Jia Yang ◽  
Tao Xin ◽  
Song Xue ◽  
...  
Keyword(s):  
Dna Methyltransferase ◽  
Goodness Of Fit ◽  
Clinical Target Volume ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
High Grade Glioma ◽  
Target Volume ◽  
Tumor Location ◽  
High Grade ◽  
Clinical Trial Registry

Abstract Introduction In this study, we performed a consecutive macropathologic analysis to assess microscopic extension (ME) in high-grade glioma (HGG) to determine appropriate clinical target volume (CTV) margins for radiotherapy. Materials and methods The study included HGG patients with tumors located in non-functional areas, and supratotal resection was performed. The ME distance from the edge of the tumor to the microscopic tumor cells surrounding brain tissue was measured. Associations between the extent of ME and clinicopathological characteristics were evaluated by multivariate linear regression (MVLR) analysis. An ME predictive model was developed based on the MVLR model. Results Between June 2017 and July 2019, 652 pathologic slides obtained from 30 HGG patients were analyzed. The mean ME distance was 1.70 cm (range, 0.63 to 2.87 cm). The MVLR analysis identified that pathologic grade, subventricular zone (SVZ) contact and O6-methylguanine-DNA methyltransferase (MGMT) methylation, isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion status were independent variables predicting ME (all P < 0.05). A multivariable prediction model was developed as follows: YME = 0.672 + 0.513XGrade + 0.380XSVZ + 0.439XMGMT + 0.320XIDH + 0.333X1p/19q. The R-square value of goodness of fit was 0.780. The receiver operating characteristic curve proved that the area under the curve was 0.964 (P < 0.001). Conclusion ME was heterogeneously distributed across different grades of gliomas according to the tumor location and molecular marker status, which indicated that CTV delineation should be individualized. The model could predict the ME of HGG, which may help clinicians determine the CTV for individual patients. Trial registration The trial was registered with Chinese Clinical Trial Registry (ChiCTR2100046106). Registered 4 May 2021-Retrospectively registered.

OS03.4.A Irradiation of the subventricular and subgranular zone and overall survival in high-grade glioma patients

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii6-ii6
Author(s):  
D Bruil ◽  
S David ◽  
S Nagtegaal ◽  
J Verhoeff
Keyword(s):  
Overall Survival ◽  
Confidence Interval ◽  
High Grade Glioma ◽  
Radiotherapy Planning ◽  
Intracranial Volume ◽  
High Grade ◽  
Subgranular Zone ◽  
Median Dose ◽  
Repair Capacity ◽  
The Mean

Abstract BACKGROUND Previous research has shown that neural stem cells (NSCs) in the subventricular zone (SVZ) may support the growth of glioma by recruiting new cells to the tumor. NSCs are located in the SVZ as well as in the subgranular zone (SGZ) of the hippocampus, the two neurogenic niches of the brain. This might indicate that irradiation of the SVZ and SGZ, and thereby damaging NSCs, reduces tumor growth and improves overall survival (OS). However, irradiation may also inhibit the repair capacity of healthy brain tissue by these neurogenic niches. Therefore, we investigated the effects of SVZ and SGZ irradiation dose on OS, in a cohort of high-grade glioma patients. MATERIAL AND METHODS We have retrospectively selected 221 patients (2014–2020) with WHO grade III and IV gliomas that underwent radiotherapy. Next to clinical baseline characteristics, T1 weighted MRI- and CT-images were collected. The SVZ and SGZ regions on the individual T1 images were delineated via non-linear registration of brain atlases. SVZ labels were created in 0.5mm isotropic MNI T1 and T2 templates, while SGZ atlas labels were available via the Hippocampus and Subfields CoBrA atlas. Next, the mean dose from the acquired SVZ and SGZ labels were extracted. The relationship between SVZ doses, SGZ doses and OS were examined using the Cox proportional hazards model and the Kaplan-Meier method (using the Log Rank test for significance). RESULTS For the mean dose in the SVZ, the hazard ratio (HR) was 1.024 per Gy (P = 0.002, [95% confidence interval, 1.009–1.040]) and the mean SGZ dose had a HR of 1.021 per Gy (P&lt; 0.001, [95% confidence interval, 1.012–1.031]). These results were then corrected for the following covariates: sex, age, total intracranial volume and extent of surgery. This resulted in a HR of 1.031 per Gy (P = 0,001, [95% confidence interval, 1.014–1.050]) for the mean SVZ dose, and a HR of 1.025 per Gy (P&lt; 0.001, [95% confidence interval, 1.015–1.036]) for the mean SGZ dose. Patients whose SVZ received greater than the median SVZ dose (= 31.3 Gy) showed a significant decrease in OS compared to patients who received less than the median dose (10.7 months vs 13.5 months median OS, P = 0.001). Patients whose SGZ received greater than the median SGZ dose (= 31.9) showed a significant decrease in OS compared to patients who received less than the median dose (10.7 months vs 15.1 months median OS, P&lt; 0.001). CONCLUSION Here, we present a large cohort of high-grade glioma patients, in which we show a statistically significant decrease in overall survival with increasing radiation dose on the SGZ and SVZ. This correlation suggests that both neurogenic niches might need to be spared during radiotherapy treatment to improve overall survival even in high-grade glioma patients. Modern radiotherapy planning and delivery options are available to implement this.

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