Evidence-Based Diagnostic Algorithm for Glioma: Analysis of the Results of Pathology Panel Review and Molecular Parameters of EORTC 26951 and 26882 Trials

2015 ◽  
Vol 33 (17) ◽  
pp. 1943-1950 ◽  
Author(s):  
Johan M. Kros ◽  
Karin Huizer ◽  
Aurelio Hernández-Laín ◽  
Gianluca Marucci ◽  
Alex Michotte ◽  
...  
Keyword(s):  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Diagnostic Algorithm ◽  
Virtual Microscopy ◽  
Molecular Data ◽  
Conditional Inference ◽  
Diagnostic Process ◽  
Egfr Amplification ◽  
Molecular Parameters ◽  
Panel Review

Purpose With the rapid discovery of prognostic and predictive molecular parameters for glioma, the status of histopathology in the diagnostic process should be scrutinized. Our project aimed to construct a diagnostic algorithm for gliomas based on molecular and histologic parameters with independent prognostic values. Methods The pathology slides of 636 patients with gliomas who had been included in EORTC 26951 and 26882 trials were reviewed using virtual microscopy by a panel of six neuropathologists who independently scored 18 histologic features and provided an overall diagnosis. The molecular data for IDH1, 1p/19q loss, EGFR amplification, loss of chromosome 10 and chromosome arm 10q, gain of chromosome 7, and hypermethylation of the promoter of MGMT were available for some of the cases. The slides were divided in discovery (n = 426) and validation sets (n = 210). The diagnostic algorithm resulting from analysis of the discovery set was validated in the latter. Results In 66% of cases, consensus of overall diagnosis was present. A diagnostic algorithm consisting of two molecular markers and one consensus histologic feature was created by conditional inference tree analysis. The order of prognostic significance was: 1p/19q loss, EGFR amplification, and astrocytic morphology, which resulted in the identification of four diagnostic nodes. Validation of the nodes in the validation set confirmed the prognostic value (P < .001). Conclusion We succeeded in the creation of a timely diagnostic algorithm for anaplastic glioma based on multivariable analysis of consensus histopathology and molecular parameters.

scholarly journals GCT-15. INTEGRATED CLINICAL, HISTOPATHOLOGICAL, AND MOLECULAR DATA ANALYSIS OF 190 CENTRAL NERVOUS SYSTEM GERM CELL TUMORS FROM THE IGCT CONSORTIUM

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii330-iii331
Author(s):  
Hirokazu Takami ◽  
Koichi Ichimura ◽  
Kohei Fukuoka ◽  
Akitake Mukasa ◽  
Nobuhito Saito ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Basal Ganglia ◽  
Pineal Gland ◽  
Germ Cell ◽  
Prognostic Significance ◽  
Germ Cell Tumors ◽  
Molecular Data ◽  
Molecular Heterogeneity ◽  
Intracranial Germ Cell Tumor

Abstract BACKGROUND We integrated clinical, histopathological, and molecular data of central nervous system germ cell tumors to provide insights into their management. METHODS Data from the Intracranial Germ Cell Tumor Genome Analysis Consortium were reviewed. A total of 190 cases were classified as primary GCTs based on central pathological reviews. RESULTS All but one of the cases that were bifocal (neurohypophysis and pineal glands) and cases with multiple lesions including neurohypophysis or pineal gland were germinomas (34 of 35). Age was significantly higher in patients with germinoma than other histologies. Comparison between tumor marker and histopathological diagnoses showed that 18.2% of histopathologically diagnosed germinomas were marker-positive and 6.1% of non-germinomatous GCTs were marker-negative, suggesting a limitation in the utility of markers or histopathology alone using small specimens for diagnosis. Comparison between local and central histopathological diagnoses revealed a discordance of 12.7%. Discordance was significantly less frequent in biopsy cases, implying difficulty in detecting all histopathological components of heterogeneous GCTs. Germinomas at the typical sites (neurohypophysis or pineal gland) showed a better PFS than those at atypical sites (p=0.03). A molecular-clinical association study revealed frequent MAPK pathway mutations in males (51.4 vs 14.3 %, p=0.007), and PI3K/mTOR pathway mutations in basal ganglia cases (p=0.004). Basal ganglia cases also had frequent chromosomal losses. Some chromosomal aberrations (2q, 8q gain, 5q, 9p/q, 13q, 15q loss) showed potential prognostic significance. CONCLUSIONS These in-depth findings of this study regarding the clinical and molecular heterogeneity will increase our understanding of the pathogenesis of this enigmatic tumor.

scholarly journals PATH-10. RELATIONSHIP BETWEEN CYTOGENETIC COMPLEXITY AND PERITUMORAL EDEMA IN HIGH-GRADE ASTROCYTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi145-vi145
Author(s):  
Kyoung Su Sung ◽  
Young-Jin Song ◽  
Jin-Yeong Han ◽  
Ki-Uk Kim
Keyword(s):  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
Chromosome 7 ◽  
High Grade ◽  
Peritumoral Edema ◽  
Complex Karyotype ◽  
Egfr Amplification ◽  
High Grade Astrocytoma ◽  
Average Survival ◽  
Endothelial Growth Factor

Abstract The purpose of the study is to reveal the association of cytogenetic complexity and peritumoral edema volume (PTEV) and its prognostic significance in high-grade astrocytoma patients by culturing patient tumor cells. Twenty-seven high-grade astrocytoma patients were divided into three groups according to karyotype complexity: normal, non-complex karyotype (NCK), and complex karyotype (CK). Endothelial growth factor receptor (EGFR) amplification was detected by FISH, and its association with chromosome 7 abnormalities was analyzed. Mean PTEV of each group was compared by ANOVA to evaluate the relationship between PTEV and cytogenetic complexity. The PTEV of patients in normal (n=6), NCK (n=8), and CK (n=13) groups were 24.52±17.73, 34.26±35.04, and 86.31±48.7 cm3, respectively (P=0.005). Ten out of 11 patients with EGFR amplification showed abnormalities in chromosome 7. The mean PTEV of EGFR-amplified and non-amplified groups were 80.4±53.7 and 41.3±37.9 cm3, respectively (P=0.035). The average survival of patients with PTEV less than 90 cm3 was 30.52±26.11 months, while in patients with PTEVs over or equal to 90 cm3, it was 10.83±5.53 months (P=0.007). The results show an association of complex karyotype with the PTEV of high-grade astrocytoma. EGFR amplification plays a significant role in the formation of peritumoral edema, causing PTEV to increase, which is related with survival. This implies that cytogenetic karyotype can be applied as a prognostic factor.

Comparison of clinicopathological features and outcomes in patients with primary leiomyosarcoma of bone and soft tissue.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e23526-e23526
Author(s):  
Alan T. Blank ◽  
Charles Gusho ◽  
Steven Gitelis
Keyword(s):  
Soft Tissue ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Distant Metastases ◽  
High Grade ◽  
Seer Database ◽  
Inclusion Criteria ◽  
Rare Malignancy ◽  
Primary Leiomyosarcoma

e23526 Background: Leiomyosarcoma is a rare malignancy that may occur in bone. This investigation described the characteristics and outcomes of primary leiomyosarcoma of bone (PLB) compared to soft tissue leiomyosarcoma (SLMS). Methods: This study was a retrospective review using the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2016. Continuous and categorial variables were described, and Cox regression were used to identify factors of prognostic significance. Results: Seven thousand five-hundred two patients met inclusion criteria. Seventy-four (1%) were PLB and 7428 (99%) were SLMS. On multivariable analysis for high-grade SLMS radiation (neoadjuvant: HR, 0.56; 95% CI, 0.4-0.8; p = 0.003, and adjuvant: HR, 0.75; 95% CI, 0.6-0.9; p = 0.008) and surgery (procedure specific) improved DSS, while age (HR, 1.013; 95% CI, 1.0-1.1; p < 0.001), tumor size greater than or equal to 5 cm (HR, 3.16; 95% CI, 2.3-4.2; p < 0.001), abdomen/pelvis/trunk/thorax tumors (HR, 1.31; 95% CI, 1.1-1.6; p = 0.006), and distant metastases at presentation (HR, 2.6; 95% CI, 2.1-3.3; p < 0.001) negatively influenced DSS. Conclusions: Radiation and surgery positively influence survival in high-grade SLMS while chemotherapy appears to have no benefit. Surgery alone appears to lower the mortality risk in PLB.

scholarly journals Distinct clinical and biological characteristics of acute myeloid leukemia with higher expression of long noncoding RNA KIAA0125

2020 ◽  
Author(s):  
Yu-Hung Wang ◽  
Chien-Chin Lin ◽  
Chia-Lang Hsu ◽  
Sheng-Yu Hung ◽  
Chi-Yuan Yao ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Noncoding Rna ◽  
De Novo ◽  
Remission Rate ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Disease Free Survival ◽  
Biological Characteristics ◽  
Acute Myeloid

AbstractExpression of long non-coding RNA KIAA0125 has been incorporated in various gene expression signatures for prognostic prediction in acute myeloid leukemia (AML) patients, yet its functions and clinical significance remain unclear. This study aimed to investigate the clinical and biological characteristics of AML bearing different levels of KIAA0125. We profiled KIAA0125 expression levels in bone marrow cells from 347 de novo AML patients and found higher KIAA0125 expression was closely associated with RUNX1 mutation, but inversely correlated with t(8;21) and t(15;17) karyotypes. Among the 227 patients who received standard chemotherapy, those with higher KIAA0125 expression had a lower complete remission rate, shorter overall survival (OS) and disease-free survival (DFS) than those with lower expression. The prognostic significance was validated in both TCGA and GSE12417 cohorts. Subgroup analyses showed that higher KIAA0125 expression also predicted shorter DFS and OS in patients with normal karyotype or non-M3 AML. In multivariable analysis, higher KIAA0125 expression remained an adverse risk factor independent of age, WBC counts, karyotypes, and mutation patterns. Bioinformatics analyses revealed that higher KIAA0125 expression was associated with hematopoietic and leukemic stem cell signatures and ATP-binding cassette transporters, two predisposing factors for chemoresistance.

scholarly journals Prognostic role of GPER/Ezrin in triple-negative breast cancer is associated with menopausal status

2019 ◽  
Vol 8 (6) ◽  
pp. 661-671 ◽  
Author(s):  
Shuang Ye ◽  
Yuanyuan Xu ◽  
Jiehao Li ◽  
Shuhui Zheng ◽  
Peng Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cox Regression ◽  
Menopausal Status ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Survival Prognosis ◽  
Kaplan Meier

The role of G protein-coupled estrogen receptor 1 (GPER) signaling, including promotion of Ezrin phosphorylation (which could be activated by estrogen), has not yet been clearly identified in triple-negative breast cancer (TNBC). This study aimed to evaluate the prognostic value of GPER and Ezrin in TNBC patients. Clinicopathologic features including age, menopausal status, tumor size, nuclear grade, lymph node metastasis, AJCC TNM stage, and ER, PR and HER-2 expression were evaluated from 249 TNBC cases. Immunohistochemical staining of GPER and Ezrin was performed on TNBC pathological sections. Kaplan–Meier analyses, as well as logistic regressive and Cox regression model tests were applied to evaluate the prognostic significance between different subgroups. Compared to the GPER-low group, the GPER-high group exhibited higher TNM staging (P = 0.021), more death (P < 0.001), relapse (P < 0.001) and distant events (P < 0.001). Kaplan–Meier analysis showed that GPER-high patients had a decreased OS (P < 0.001), PFS (P < 0.001), LRFS (P < 0.001) and DDFS (P < 0.001) than GPER-low patients. However, these differences in prognosis were not statistically significant in post-menopausal patients (OS, P = 0.8617; PFS, P = 0.1905; LRFS, P = 0.4378; DDFS, P = 0.2538). There was a significant positive correlation between GPER and Ezrin expression level (R = 0.508, P < 0.001) and the effect of Ezrin on survival prognosis corresponded with GPER. Moreover, a multivariable analysis confirmed that GPER and Ezrin level were both significantly associated with poor DDFS (HR: 0.346, 95% CI 0.182–0.658, P = 0.001; HR: 0.320, 95% CI 0.162–0.631, P = 0.001). Thus, overexpression of GPER and Ezrin may contribute to aggressive behavior and indicate unfavorable prognosis in TNBC; this may correspond to an individual’s estrogen levels.

Lower serum retinoic acid level for prediction of higher risk of mortality in ischemic stroke

Neurology ◽  
2019 ◽  
Vol 92 (15) ◽  
pp. e1678-e1687 ◽  
Author(s):  
Wen-Jun Tu ◽  
Han-Cheng Qiu ◽  
Yiqun Zhang ◽  
Jian-lei Cao ◽  
Hong Wang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Retinoic Acid ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Net Reclassification Improvement ◽  
Risk Of Mortality ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Cvd Mortality

ObjectiveTo explore the association between serum retinoic acid (RA) level in patients with acute ischemic stroke (AIS) and mortality risk in the 6 months after admission.MethodsFrom January 2015 through December 2016, patients admitted to 3 stroke centers in China for first-ever AIS were screened. The primary endpoint was all-cause mortality or cardiovascular disease (CVD) mortality in the 6 months after admission. The significance of serum RA level, NIH Stroke Scale score, and established risk factors in predicting mortality were determined. The integrated discrimination improvement (IDI) and net reclassification improvement (NRI) statistics were applied in statistical analysis.ResultsOf the 1,530 patients enrolled, 325 died within 6 months of admission, with an all-cause mortality of 21.2% and CVD-related mortality of 13.1%. In multivariable analysis, RA levels were expressed as quartiles with the clinical variables. The results of the second to fourth quartiles (Q2–Q4) were compared with the first quartile (Q1); RA levels showed prognostic significance, with decreased all-cause and CVD mortality of 55% and 63%, respectively. After RA was added to the existing risk factors, all-cause mortality could be better reclassified, in association with only the NRI statistic (p = 0.005); CVD mortality could be better reclassified with significance, in association with both the IDI and NRI statistics (p < 0.01).ConclusionsLow circulating levels of RA were associated with increased risk of all-cause and CVD mortality in a cohort of patients with first-incidence AIS, indicating that RA level could be a predictor independent of established conventional risk factors.

scholarly journals Cyclo-oxygenase-2 expression is associated with mean standardised uptake value on 18F-Fluorodeoxyglucose positron emission tomography in oesophageal adenocarcinoma

2019 ◽  
Vol 92 (1099) ◽  
pp. 20180668
Author(s):  
Kieran G Foley ◽  
Adam Christian ◽  
James Peaker ◽  
Christopher Marshall ◽  
Emiliano Spezi ◽  
...  
Keyword(s):  
Cox Regression ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Image Features ◽  
Oesophageal Adenocarcinoma ◽  
Metabolic Tumour Volume ◽  
Multi Centre Study ◽  
Cox Regression Analysis ◽  
Standardised Uptake Value ◽  
Cox 2

Objectives: This pilot study investigated the association of four PET image features and cyclo-oxygenase-2 (COX-2) expression in patients with oesophageal adenocarcinoma. The prognostic significance of these biomarkers was also assessed. Methods: 50 consecutive patients [median age = 68 (range 47 – 84), males = 45) with oesophageal adenocarcinoma had PET/CT staging between January 2011 and July 2015. The maximum and mean standardised uptake values (SUVmax and SUVmean), metabolic tumour volume (MTV) and tumour lesion glycolysis (TLG) were calculated from the primary tumour. Their association with COX-2 status was assessed using Mann-Whitney U tests. Kaplan-Meier and Cox regression analysis tested their prognostic significance. A p-value < 0.05 was considered statistically significant. Results: 32 tumours (64.0%) were COX-2 positive. There was a significant association between SUVmean and COX-2 status (p = 0.019). TLG (hazard ratio (HR) 1.001, 95 % confidence intervals (CI) 1.000 – 1.002, p = 0.018) was significantly associated with overall survival on multivariable analysis. Conclusions: This study investigated the association between PET image features and COX-2 expression in oesophageal adenocarcinoma. The preliminary results signal that a combination of TLG (calculated as product of MTV and SUVmean) and COX-2 status may be a strong and clinically important prognostic biomarker. Our research group are planning a prospective, multi-centre study to validate these findings. Advances in knowledge: Mean standardised uptake value (SUVmean) on PET imaging is associated with COX-2 expression in oesophageal adenocarcinoma.

scholarly journals Integrated clinical, histopathological, and molecular data analysis of 190 central nervous system germ cell tumors from the iGCT Consortium

2019 ◽  
Vol 21 (12) ◽  
pp. 1565-1577 ◽  
Author(s):  
Hirokazu Takami ◽  
Kohei Fukuoka ◽  
Shintaro Fukushima ◽  
Taishi Nakamura ◽  
Akitake Mukasa ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Basal Ganglia ◽  
Pineal Gland ◽  
Germ Cell ◽  
Prognostic Significance ◽  
Germ Cell Tumors ◽  
Molecular Data ◽  
Molecular Heterogeneity ◽  
Intracranial Germ Cell Tumor

Abstract Background We integrated clinical, histopathological, and molecular data of central nervous system germ cell tumors to provide insights into their management. Methods Data from the Intracranial Germ Cell Tumor Genome Analysis (iGCT) Consortium were reviewed. A total of 190 cases were classified as primary germ cell tumors (GCTs) based on central pathological reviews. Results All but one of the cases that were bifocal (neurohypophysis and pineal glands) and cases with multiple lesions including neurohypophysis or pineal gland were germinomas (34 of 35). Age was significantly higher in patients with germinoma than other histologies. Comparison between tumor marker and histopathological diagnoses showed that 18.2% of histopathologically diagnosed germinomas were marker positive and 6.1% of non-germinomatous GCTs were marker negative, suggesting a limitation in the utility of markers or histopathology alone using small specimens for diagnosis. Comparison between local and central histopathological diagnoses revealed a discordance of 12.7%. Discordance was significantly less frequent in biopsy cases, implying difficulty in detecting all histopathological components of heterogeneous GCTs. Germinomas at the typical sites (neurohypophysis or pineal gland) showed a better progression-free survival than those at atypical sites (P = 0.03). A molecular clinical association study revealed frequent mitogen-activated protein kinase (MAPK) pathway mutations in males (51.4% vs 14.3%, P = 0.007), and phosphatidylinositol-3 kinase/mammalian target of rapamycin (PI3K/mTOR) pathway mutations in basal ganglia cases (P = 0.004). Basal ganglia cases also had frequent chromosomal losses. Some chromosomal aberrations (2q, 8q gain, 5q, 9p/q, 13q, 15q loss) showed potential prognostic significance. Conclusions The in-depth findings of this study regarding clinical and molecular heterogeneity will increase our understanding of the pathogenesis of this enigmatic tumor.

scholarly journals Prognostic impact of CDKN2A/B deletion, TERT mutation, and EGFR amplification on histological and molecular IDH-wildtype glioblastoma

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Sirui Ma ◽  
Soumon Rudra ◽  
Jian L Campian ◽  
Sonika Dahiya ◽  
Gavin P Dunn ◽  
...  
Keyword(s):  
Cox Regression ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Prognostic Impact ◽  
Egfr Amplification ◽  
Molecular Alterations ◽  
Kaplan Meier ◽  
P 16 ◽  
Grade Ii ◽  
Tert Mutation

Abstract Background We aimed to evaluate the clinical outcomes of molecular glioblastoma (mGBM) as compared to histological GBM (hGBM) and to determine the prognostic impact of TERT mutation, EGFR amplification, and CDKN2A/B deletion on isocitrate dehydrogenase (IDH)-wildtype GBM. Methods IDH-wildtype GBM patients treated with radiation therapy (RT) between 2012 and 2019 were retrospectively analyzed. mGBM was defined as grade II-III IDH-wildtype astrocytoma without histological features of GBM but with one of the following molecular alterations: TERT mutation, EGFR amplification, or combination of whole chromosome 7 gain and whole chromosome 10 loss. Overall survival (OS) and progression-free survival (PFS) were calculated from RT and analyzed using the Kaplan–Meier method. Multivariable analysis (MVA) was performed using Cox regression to identify independent predictors of OS and PFS. Results Of the 367 eligible patients, the median follow-up was 11.7 months. mGBM and hGBM did not have significantly different OS (median: 16.6 vs 13.5 months, respectively, P = .16), nor PFS (median: 11.7 vs 7.3 months, respectively, P = .08). However, mGBM was associated with better OS (hazard ratio [HR] 0.50, 95% CI 0.29–0.88) and PFS (HR 0.43, 95% CI 0.26–0.72) than hGBM after adjusting for known prognostic factors on MVA. CDKN2A/B deletion was associated with worse OS (HR 1.57, 95% CI 1.003–2.46) and PFS (HR 1.57, 95% CI 1.04–2.36) on MVA, but TERT mutation and EGFR amplification were not. Conclusion Criteria for mGBM may require further refinement and validation. CDKN2A/B deletion, but not TERT mutation or EGFR amplification, may be an independent prognostic biomarker for IDH-wildtype GBM patients.

scholarly journals Prognostic significance of patent foramen ovale in anticoagulated patients with atrial fibrillation

Open Heart ◽  
2020 ◽  
Vol 7 (1) ◽  
pp. e001229
Author(s):  
Rowlens M Melduni ◽  
Waldemar E Wysokinski ◽  
Zhenzhen Wang ◽  
Bernard J Gersh ◽  
Samuel J Asirvatham ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischaemic Stroke ◽  
Patent Foramen Ovale ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Multivariable Analysis ◽  
Contrast Study ◽  
Foramen Ovale ◽  
Obstructive Sleep ◽  
Increased Risk

ObjectivePrevious studies have postulated a causal role of patent foramen ovale (PFO) in the aetiology of embolic stroke in the general population. We hypothesised that the presence of concomitant PFO and atrial fibrillation (AF) will add incremental risk of ischaemic stroke to that linked to AF alone.MethodsWe analysed data on 3069 consecutive patients (mean age 69.4±12.2 years; 67.1% men) undergoing transoesophageal echocardiography-guided electrical cardioversion (ECV) for AF between May 2000 and March 2012. PFO was identified by colour Doppler and agitated saline contrast study. All patients were followed up after ECV for first documentation of ischaemic stroke. Outcomes were compared using Cox regression models.ResultsThe prevalence of PFO was 20.0% and the shunt direction was left-to-right in the majority of patients (71.4%). Patients with PFO had a higher frequency of obstructive sleep apnoea (21.7% vs 17.1%, p=0.01) and higher mean peak left atrial appendage emptying velocity (38.3±21.8 vs 36.1±20.4 cm/s; p=0.04) compared with those without PFO. Otherwise, baseline characteristics were similar between groups. During a mean follow-up period of 7.3±4.6 years, 214 patients (7.0%) had ischaemic stroke. Multivariable analysis showed no significant association between PFO and ischaemic stroke (HR, 0.82 (95% CI 0.57 to 1.18)). PFO shunt direction was strongly associated with stroke: HR, 1.91 (95% CI 1.16 to 3.16) for right-to-left shunt and HR, 0.58 (95% CI 0.36 to 0.93) for left-to-right shunt.ConclusionsThe presence of concurrent PFO in this largely anticoagulated group of patients with AF was not associated with increased risk of ischaemic stroke.

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