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 >0.05 were included preliminarily, for which bivariate Cox proportional hazards regression models were employed. Twenty-two variants with P< 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< 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 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.

scholarly journals Homotopic functional connectivity disruptions in glioma patients are associated with tumor malignancy and overall survival

2021 ◽  
Author(s):  
Andy G S Daniel ◽  
Carl D Hacker ◽  
John J Lee ◽  
Donna Dierker ◽  
Joseph B Humphries ◽  
...  
Keyword(s):  
Overall Survival ◽  
Functional Connectivity ◽  
Healthy Subjects ◽  
High Grade Glioma ◽  
Tumor Grade ◽  
World Health ◽  
Low Grade ◽  
High Grade ◽  
Healthy Controls ◽  
Who Grade

Abstract Background Gliomas exhibit widespread bilateral functional connectivity (FC) alterations that may be associated with tumor grade. Limited studies have examined the connection-level mechanisms responsible for these effects. Given the typically strong FC observed between mirroring/homotopic brain regions in healthy subjects, we hypothesized that homotopic connectivity (HC) is altered in low-grade and high-grade glioma patients and the extent of disruption is associated with tumor grade and predictive of overall survival (OS) in a cohort of de novo high-grade glioma (World Health Organization [WHO] grade 4) patients. Methods We used a mirrored FC-derived cortical parcellation to extract blood-oxygen-level-dependent (BOLD) signals and to quantify FC differences between homotopic pairs in normal-appearing brain in a retrospective cohort of glioma patients and healthy controls. Results Fifty-nine glioma patients (WHO grade 2, n = 9; grade 4 = 50; mean age, 57.5 years) and thirty healthy subjects (mean age, 65.9 years) were analyzed. High-grade glioma patients showed lower HC compared to low-grade glioma patients and healthy controls across several cortical locations and resting-state networks. Connectivity disruptions were also strongly correlated with hemodynamic lags between homotopic regions. Finally, in high-grade glioma patients with known survival times (n = 42), HC in somatomotor and dorsal attention networks were significantly correlated with OS. Conclusions These findings demonstrate an association between tumor grade and HC alterations that may underlie global FC changes and provide prognostic information.

scholarly journals Effectiveness of BRAF inhibitors in patients with BRAF V600 mutation positive glioma: a systematic review

2019 ◽  
Vol 21 (Supplement_4) ◽  
pp. iv14-iv14
Author(s):  
Ian Yao ◽  
Sarah Dawson ◽  
Julian Higgins ◽  
Luke McGuinness ◽  
Alexandra McAleenan ◽  
...  
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Objective Response ◽  
Braf Inhibitor ◽  
High Grade Glioma ◽  
Low Grade ◽  
High Grade ◽  
Braf Inhibitors ◽  
Duration Of Treatment ◽  
Braf V600 Mutation

Abstract Background BRAF inhibitor treatment with vemurafenib and dabrafenib have produced significant increases in median overall survival for BRAF V600 mutation-positive melanoma patients and are in wide clinical use. BRAF inhibitors have also been used in an ad hoc fashion in BRAF V600 mutation-positive glioma in a number of glioma subtypes with varying prognoses. Methods An electronic search was performed on MEDLINE and Embase on February 1, 2019 to identify studies of any design that reported the outcome of patients with BRAF V600 mutation-positive glioma treated with BRAF inhibitors. Data was collected for demographic information, tumour information (type and grading), BRAF mutation type, prior treatment regimens, type of BRAF inhibitor, dose and duration of treatment, best objective response, progression free survival (PFS), overall survival (OS), glioma specific symptomatic relief and adverse events. Preliminary Results Seventy-nine case reports, case series and single arm cohort studies with a total of 286 patients were included. Duration of treatment was available for 197 patients and varied from 0.1 to 54 months, with 104 patients still undergoing treatment at the time of publication. Progression occurred in 158 patients (including both low-grade and high-grade glioma) at between 0.805 and 36 months following the start of treatment. 34 people died, at between 0.329 and 40.1 months following the start of treatment. Conclusions Our systematic review shows varying clinical effectiveness of BRAF inhibitors in BRAF V600 mutation-positive glioma depending on low-grade or high-grade glioma. This evidence may inform future trials of BRAF inhibitors for glioma patients.

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.

scholarly journals Prognostic significance of CEA, Ki67 and p53 in pseudomyxoma peritonei of appendiceal origin

2021 ◽  
Vol 49 (6) ◽  
pp. 030006052110222
Author(s):  
Fengcai Yan ◽  
Feng Shi ◽  
Xinbao Li ◽  
Hong Chang ◽  
Mulan Jin ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pseudomyxoma Peritonei ◽  
Histological Grade ◽  
Prognostic Significance ◽  
Mucinous Carcinoma ◽  
Cox Proportional Hazards ◽  
Nuclear Antigen ◽  
Low Grade ◽  
High Grade ◽  
Biological Behaviour

Objective To determine the levels of carcinoembryonic antigen (CEA), proliferating nuclear antigen Ki67 and p53 in pseudomyxoma peritonei (PMP) of appendiceal origin and to correlate the levels with clinicopathological characteristics and overall survival. Methods This retrospective study collected data on clinicopathological features and immunohistochemical staining of CEA, Ki67 and p53 in patients with PMP of appendiceal origin. Overall survival was evaluated using Kaplan–Meier plots. Median survival time was estimated by Log-rank tests. Potential prognostic factors were evaluated by Cox proportional hazards regression models. Results A total of 141 patients with PMP of appendiceal origin were enrolled in the study with a median age of 54 years. Of these, 93 (66.0%) were diagnosed with low-grade mucinous carcinoma, 43 (30.5%) with high-grade mucinous carcinoma and five (3.5%) with high-grade with signet ring cells. CEA exhibited ubiquitous immunopositivity in most cases and was not associated with overall survival. Ki67 labelling index (LI) and p53 status were related to histological grade and overall survival. The main pathological indicators affecting survival included histological grade, lymph node involvement, angiolymphatic invasion, Ki67 LI and p53. Conclusion Combined analysis of high Ki67 LI and aberrant p53 may provide the basis for evaluating the biological behaviour of PMP and predicting clinical outcome.

scholarly journals Regional Recurrences and Hyams Grade in Esthesioneuroblastoma

2020 ◽  
Author(s):  
Hedyeh Ziai ◽  
Eugene Yu ◽  
Ilan Weinreb ◽  
Bayardo Perez-Ordonez ◽  
Christopher M. K. L. Yao ◽  
...  
Keyword(s):  
Overall Survival ◽  
Small Sample Size ◽  
Tertiary Care ◽  
Small Sample ◽  
Oncologic Outcomes ◽  
Low Grade ◽  
High Grade ◽  
Grade Versus ◽  
Regional Failure ◽  
The Impact

Abstract Objective The aim of this study is to determine if Hyams grade may help predict which patients with esthesioneuroblastoma (ENB) tumors are likely to develop regional recurrences, and to determine the impact of tumor extent on regional failure in ENB patients without evidence of nodal disease at presentation. Design The study was designed as a retrospective review for ENB patients. Settings The study was prepared at tertiary care academic center for ENB patients. Participants Patients with ENB were included in the study. Main Outcome Measures  Oncologic outcomes (5-year regional and locoregional control (LRC) and overall survival) in patients with Hyams low grade versus high grade. Oncologic outcomes based on radiographic disease extent. Results A total of 43 patients were included. Total 25 patients (58%) had Hyams low-grade tumor, and 18 (42%) had high-grade tumor. Of the 34 patients without regional disease at presentation, 8 (24%) were treated with elective nodal radiation. There were no statistically significant differences in 5-year regional control in the Hyams low-grade versus high-grade groups (78 vs. 89%; p = 0.4). The 5-year LRC rates in patients with low grade versus high grade were 73 versus 89% (p = 0.6). The 5-year overall survival rates in patients with low-grade versus high-grade tumors were 86 versus 63% (p = 0.1). Radiographic extension of disease into the olfactory groove, olfactory nerve, dura, and periorbita were statistically associated with decreased 5-year overall survival (5-year OS 49 vs. 91% [p = 0.04], 49 vs. 91% [p = 0.04], 44 vs. 92% [p = 0.02], and 44 vs. 80% [p = 0.04], respectively). Conclusion ENBs are associated with a risk of regional failure. The current analysis suggests that Hyams low-grade and high-grade malignancies have comparable rates of early and delayed regional recurrences, although small sample size may limit our conclusions.

scholarly journals Trace Amine-Associated Receptor 1 (TAAR1) Is a Positive Prognosticator for Epithelial Ovarian Cancer

2021 ◽  
Vol 22 (16) ◽  
pp. 8479
Author(s):  
Tilman L. R. Vogelsang ◽  
Aurelia Vattai ◽  
Elisa Schmoeckel ◽  
Till Kaltofen ◽  
Anca Chelariu-Raicu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Epithelial Ovarian Cancer ◽  
Tnm Classification ◽  
Rank Correlation ◽  
University Hospital ◽  
Cancer Tissue ◽  
Low Grade ◽  
High Grade ◽  
Trace Amine

Trace amine-associated receptor 1 (TAAR1) is a Gαs- protein coupled receptor that plays an important role in the regulation of the immune system and neurotransmission in the CNS. In ovarian cancer cell lines, stimulation of TAAR1 via 3-iodothyronamine (T1AM) reduces cell viability and induces cell death and DNA damage. Aim of this study was to evaluate the prognostic value of TAAR1 on overall survival of ovarian carcinoma patients and the correlation of TAAR1 expression with clinical parameters. Ovarian cancer tissue of n = 156 patients who were diagnosed with epithelial ovarian cancer (serous, n = 110 (high-grade, n = 80; low-grade, n = 24; unknown, n = 6); clear cell, n = 12; endometrioid, n = 21; mucinous, n = 13), and who underwent surgery at the Department of Obstetrics and Gynecology, University Hospital of the Ludwig-Maximilians University Munich, Germany between 1990 and 2002, were analyzed. The tissue was stained immunohistochemically with anti-TAAR1 and evaluated with the semiquantitative immunoreactive score (IRS). TAAR1 expression was correlated with grading, FIGO and TNM-classification, and analyzed via the Spearman’s rank correlation coefficient. Further statistical analysis was obtained using nonparametric Kruskal-Wallis rank-sum test and Mann-Whitney-U-test. This study shows that high TAAR1 expression is a positive prognosticator for overall survival in ovarian cancer patients and is significantly enhanced in low-grade serous carcinomas compared to high-grade serous carcinomas. The influence of TAAR1 as a positive prognosticator on overall survival indicates a potential prognostic relevance of signal transduction of thyroid hormone derivatives in epithelial ovarian cancer. Further studies are required to evaluate TAAR1 and its role in the development of ovarian cancer.

scholarly journals Impact of Pathological Stratification on the Clinical Outcomes of Advanced Well-Differentiated/Dedifferentiated Liposarcoma Treated with Trabectedin

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1453
Author(s):  
Chiara Fabbroni ◽  
Giovanni Fucà ◽  
Francesca Ligorio ◽  
Elena Fumagalli ◽  
Marta Barisella ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Proportional Hazards ◽  
Case Series ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Low Grade ◽  
High Grade ◽  
Retrospective Case ◽  
Well Differentiated ◽  
The Impact

Background. We previously showed that grading can prognosticate the outcome of retroperitoneal liposarcoma (LPS). In the present study, we aimed to explore the impact of pathological stratification using grading on the clinical outcomes of patients with advanced well-differentiated LPS (WDLPS) and dedifferentiated LPS (DDLPS) treated with trabectedin. Patients: We included patients with advanced WDLPS and DDLPS treated with trabectedin at the Fondazione IRCCS Istituto Nazionale dei Tumori between April 2003 and November 2019. Tumors were categorized in WDLPS, low-grade DDLPS, and high-grade DDLPS according to the 2020 WHO classification. Patients were divided in two cohorts: Low-grade (WDLPS/low-grade DDLPS) and high-grade (high-grade DDLPS). Results: A total of 49 patients were included: 17 (35%) in the low-grade cohort and 32 (65%) in the high-grade cohort. Response rate was 47% in the low-grade cohort versus 9.4% in the high-grade cohort (logistic regression p = 0.006). Median progression-free survival (PFS) was 13.7 months in the low-grade cohort and 3.2 months in the high-grade cohort. Grading was confirmed as an independent predictor of PFS in the Cox proportional-hazards regression multivariable model (adjusted hazard ratio low-grade vs. high-grade: 0.45, 95% confidence interval: 0.22–0.94; adjusted p = 0.035). Conclusions: In this retrospective case series, sensitivity to trabectedin was higher in WDLPS/low-grade DDLPS than in high-grade DDLPS. If confirmed in larger series, grading could represent an effective tool to personalize the treatment with trabectedin in patients with advanced LPS.

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