scholarly journals High-dose radiation associated with improved survival in IDH-wildtype low-grade glioma

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Shuai Liu ◽  
Yanwei Liu ◽  
Guanzhang Li ◽  
Jin Feng ◽  
Li Chen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Analysis ◽  
Radiation Dose ◽  
Frontal Lobe ◽  
Low Grade Glioma ◽  
Molecular Characteristics ◽  
High Dose ◽  
Low Grade ◽  
Multivariate Survival ◽  
Dose Radiation

Abstract Background As molecular advances have deepened the knowledge on low-grade glioma (LGG), we investigated the effect of higher radiation dose on the survival of IDH-wildtype (IDHwt) LGG. Methods In the current study, 52 IDHwt LGG patients who received radiotherapy were enrolled from the Chinese Glioma Genome Atlas dataset. Radiation doses > 54 Gy were defined as high-dose, whereas doses ≤ 54 Gy were defined as low-dose. We performed univariate and multivariate survival analyses to examine the prognostic role of high-dose radiotherapy. Results In total, the radiation dose ranged from 48.6 Gy to 61.2 Gy, with a median of 55.8 Gy, and 31 patients were grouped into high-dose radiation. Univariate survival analysis indicated that high-dose radiotherapy (p = 0.015), tumors located in the frontal lobe (p = 0.009), and pathology of astrocytoma (p = 0.037) were significantly prognostic factors for overall survival. In multivariate survival analysis, high-dose radiotherapy (p = 0.028) and tumors located in the frontal lobe (p = 0.016) were independently associated with better overall survival. Conclusions In conclusion, high-dose radiotherapy independently improved the survival of IDHwt LGG. This can guide treatments for glioma with known molecular characteristics.

High-dose Radiation Associated with Improved Survival in IDH-wildtype Low-grade Glioma

2021 ◽  
Author(s):  
Shuai Liu ◽  
Yanwei Liu ◽  
Guanzhang Li ◽  
Jin Feng ◽  
Li Chen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Analysis ◽  
Radiation Dose ◽  
Frontal Lobe ◽  
Low Grade Glioma ◽  
Molecular Characteristics ◽  
High Dose ◽  
Low Grade ◽  
Multivariate Survival ◽  
Dose Radiation

Abstract PurposeAs molecular advances have deepened the knowledge on low-grade glioma (LGG), we investigated the effect of higher radiation dose on the survival of IDH-wildtype (IDHwt) LGG.MethodsIn the current study, 52 IDHwt LGG patients who received radiotherapy were enrolled from the Chinese Glioma Genome Atlas dataset. Radiation doses > 54 Gy were defined as high-dose, whereas doses ≤ 54 Gy were defined as low-dose. We performed univariate and multivariate survival analyses to examine the prognostic role of high-dose radiotherapy.ResultsIn total, the radiation dose ranged from 48.6 Gy to 61.2 Gy, with a median of 55.8 Gy, and 31 patients were grouped into high-dose radiation. Univariate survival analysis indicated that high-dose radiotherapy (p = 0.015), tumors located in the frontal lobe (p = 0.009), and pathology of astrocytoma (p = 0.037) were significantly prognostic factors for overall survival. In multivariate survival analysis, high-dose radiotherapy (p = 0.028) and tumors located in the frontal lobe (p = 0.016) were independently associated with better overall survival.ConclusionIn conclusion, high-dose radiotherapy independently improved the survival of IDHwt LGG. This can guide treatments for glioma with known molecular characteristics.

scholarly journals ACTR-07. LONG-TERM OUTCOMES FROM INTERGROUP NCCTG 86-72-51 (ALLIANCE): FINAL REPORT OF A PHASE III PROSPECTIVE RANDOMIZED TRIAL OF HIGH DOSE VERSUS LOW DOSE RADIATION IN ADULT SUPRATENTORIAL LOW-GRADE GLIOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi13-vi14
Author(s):  
William Breen ◽  
S Keith Anderson ◽  
Xiomara Carrero ◽  
Paul Brown ◽  
Karla Ballman ◽  
...  
Keyword(s):  
Low Dose ◽  
Low Grade Glioma ◽  
Phase Iii ◽  
High Dose ◽  
Low Grade ◽  
Tumor Diameter ◽  
Low Dose Radiation ◽  
Dose Radiation

Abstract PURPOSE To provide a final update on oncologic and cognitive outcomes of high dose versus low dose radiation for low-grade glioma. METHODS Between 1986 and 1994, 203 patients with supratentorial low grade glioma were randomized to 50.4 Gy in 28 fractions versus 64.8 Gy in 36 fractions after any degree of resection. Histologic subtype was oligodendroglioma (71%) or astrocytoma (29%). Primary outcome was overall survival (OS). Cognitive status was followed using Folstein Mini-Mental State Examination (MMSE). RESULTS For the entire cohort of 203 patients, median OS was 8.4 years (95% CI: 7.2 – 10.8). Median progression-free survival (PFS) was 5.2 years (95% CI: 4.3 – 6.6). Median follow-up is 17.2 years for the 33 patients still alive. High-dose radiation did not improve OS (15-yr OS: 22.4% vs. 24.9%, log rank p=0.978) or PFS (15-yr PFS: 15.2% vs. 9.5%, p=0.7142). OS was significantly better for patients with pre-operative tumor diameter < 5 cm (15-yr OS: 39.4% vs. 15.2%, p< 0.001), baseline MMSE > 27 (15-yr OS: 27.3% vs. 9.8%, p=0.001), and for patients who underwent gross total resection (GTR) (15-yr OS: 39.3% GTR vs. 16.4% subtotal resection vs. 24.5% biopsy only, p=0.0119). PFS was improved for patients with oligodendroglioma versus astrocytoma (15-yr PFS: 13.8% vs. 8.6%, p=0.0221). PFS was also improved for patients with pre-operative tumor diameter < 5 cm, patients who had GTR, and patients with baseline MMSE > 27. For patients who had normal MMSE at baseline, at 7 years only 1 patient (5%) had a clinically significant decrease in MMSE from the previous time point, with the remainder (95%) stable. None had decrease in MMSE at 10, 12, or 15 years. CONCLUSIONS Long-term follow-up indicates no benefit to high-dose over low-dose radiation for low-grade gliomas. Minimal late decline in cognitive function after radiation was seen by MMSE. SUPPORT: U10CA180821,U10CA180882. https://acknowledgments.alliancefound.org

scholarly journals Final report from Intergroup NCCTG 86-72-51 (Alliance): a phase III randomized clinical trial of high-dose versus low-dose radiation for adult low-grade glioma

2020 ◽  
Vol 22 (6) ◽  
pp. 830-837 ◽  
Author(s):  
William G Breen ◽  
S Keith Anderson ◽  
Xiomara W Carrero ◽  
Paul D Brown ◽  
Karla V Ballman ◽  
...  
Keyword(s):  
Low Dose ◽  
Low Grade Glioma ◽  
Gross Total Resection ◽  
High Dose ◽  
Low Grade ◽  
Tumor Diameter ◽  
Low Dose Radiation ◽  
Total Resection ◽  
Dose Radiation

Abstract Background The optimal radiation dose for adult supratentorial low-grade glioma is unknown. The aim of this study was to provide a final update on oncologic and cognitive outcomes of high-dose versus low-dose radiation for low-grade glioma. Methods Between 1986 and 1994, 203 patients with supratentorial low-grade glioma were randomized (1:1) to 50.4 Gy in 28 fractions versus 64.8 Gy in 36 fractions after any degree of resection. Results For all patients, median overall survival (OS) was 8.4 years (95% CI: 7.2–10.8). Median progression-free survival (PFS) was 5.2 years (95% CI: 4.3–6.6). Median follow-up is 17.2 years for the 33 patients still alive. High-dose radiation did not improve 15-year OS (22.4%) versus low-dose radiation (24.9%, log-rank P = 0.978) or 15-year PFS (high dose, 15.2% vs low dose, 9.5%; P = 0.7142). OS was significantly better for patients with preoperative tumor diameter &lt;5 cm and baseline Mini-Mental State Examination (MMSE) &gt;27 and who underwent gross total resection. PFS was improved for patients with oligodendroglioma versus astrocytoma, preoperative tumor diameter &lt;5 cm, patients who had gross total resection, and patients with baseline MMSE &gt;27. For patients who had normal MMSE at baseline, at 7 years only 1 patient (5%) had a clinically significant decrease in MMSE from the previous time point, with the remainder (95%) stable. None had decrease in MMSE at 10, 12, or 15 years. Conclusions Long-term follow-up indicates no benefit to high-dose over low-dose radiation for low-grade gliomas. Cognitive function appeared to be stable after radiation as measured by MMSE.

Comprehensive Analysis to Identify the Vasohibin1 (VASH1) Emerges as a Novel Prognosis Biomarker in High-Risk Low-Grade Glioma

2021 ◽  
Author(s):  
Yirizhati aili ◽  
Aierpati maimaiti ◽  
Nuersimanguli maimaitiming ◽  
Hu qin ◽  
Wenyu Ji ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Analysis ◽  
High Risk ◽  
Cancer Survival ◽  
Single Gene ◽  
Underlying Mechanism ◽  
Low Grade Glioma ◽  
Migration And Invasion ◽  
Low Grade

Abstract Background: Gliomas are complex and heterogeneous central nervous system tumors, with Low-grade Glioma (LGG)as the most common pathological type. But studies on the predictive effect of a single gene on LGG are limited. VASH1 is an epigenetic regulator with various tumors. However, the role of VASH1 in LGG remains confused. This is the first research focusing on the prognostic value and underlying mechanism of VASH1 in LGG.Methods: In this research, three independent datasets were used for mRNA-related analysis: two datasets from the TCGA and CGGA (CGGA-mRNA seq 693 and CGGA-mRNA seq 325). We analyzed and screened the clinical significance of VASH1 in overall survival and DSS of various cancers. TIMER and CIBERSORT algorithms were employed to investigate the effect of VASH1 on the tumor microenvironment. GSEA along with GO and KEGG enrichment analyses were conducted to uncover the biological functions of VASH1. In addition, a LGG patient cohort (The First Affiliated Hospital of Xinjiang Medical University) was utilized for analysis of cell infiltration by immunohistochemical, Western-blot, and qPCR; then to verify its function in regulating LGG progression in vitro.Result: In this study, the results of generalized cancer survival analysis showed that abnormal VASH1 expression was associated with poor prognosis (overall survival (OS) and disease-specific survival (DSS) in patients with adrenal cortical carcinoma (ACC), low-grade glioma (LGG), pancreatic adenocarcinoma (PAAD) and hepatocellular carcinoma (LIHC) (P<0.05). Meanwhile, VASH1 was correlated with the immune invasion, immune score, immune checkpoint, and TBM of the above four tumors, and the correlation between VASH1 expression and LGG was the strongest. In addition, we found that VASH1-mediated changes in gene expression are closely related to cell cycle, P53, Notch, and TGF-β signaling pathways. In addition, immunostaining and RT-PCR were performed on our cohort, and the results showed that VASH1 expression was significantly higher than that of para-cancer tissues (P<0.05). Kaplan-Meier survival analysis results showed that VASH1 was associated with shorter survival (OS) and shorter DFS in high-risk LGG patients (P<0.05). Multivariate Cox analysis showed that high VASH1 expression was an independent risk factor for the prognosis of LGG patients (HR=1.65, P=0.02). Finally, a high level of VASH1 was found in U-251 cell lines by in vitro cell experiments, and the migration and invasion ability of U-251 cells were significantly improved after knockdown of VASH1 (P<0.01), which further confirmed the function of VASH1.Conclusion: In conclusion, this study preliminarily indicates that VASH1 can be used as a prognostic biomarker and potential therapeutic target for LGG, and has important clinical application value.

scholarly journals P04.16 TP53 mutations in codon 273 is predictive of overall survival in astrocytoma patients

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii32-iii32
Author(s):  
H Noor ◽  
R Rapkins ◽  
K McDonald
Keyword(s):  
Overall Survival ◽  
Tp53 Mutation ◽  
Progression Free Survival ◽  
Low Grade Glioma ◽  
Low Grade ◽  
Wild Type ◽  
Mutation Status ◽  
Free Survival ◽  
Tp53 Mutations ◽  
Fresh Frozen

Abstract BACKGROUND Tumour Protein 53 (TP53) is a tumour suppressor gene that is mutated in at least 50% of human malignancies. The prevalence of TP53 mutation is much higher in astrocytomas with reports of up to 75% TP53 mutant cases. Rare cases of TP53 mutation also exist in oligodendroglial tumours (10–13%). P53 pathway is therefore an important factor in low-grade glioma tumorigenesis. Although the prognostic impact of TP53 mutations has been studied previously, no concrete concordance were reached between the studies. In this study, we investigated the prognostic effects of TP53 mutation in astrocytoma and oligodendroglioma. MATERIAL AND METHODS A cohort of 65 matched primary and recurrent fresh frozen tumours were sequenced to identify hotspot exons of TP53 mutation. Exons 1 to 10 were sequenced and pathogenic mutations were mostly predominant between Exons 4 and 8. The cohort was further expanded with 78 low grade glioma fresh frozen tissues and hotspot exons were sequenced. Selecting only the primary tumour from 65 matched tumours, a total of 50 Astrocytoma cases and 51 oligodendroglioma cases were analysed for prognostic effects of TP53. Only pathogenic TP53 mutations confirmed through COSMIC and NCBI databases were included in the over survival and progression-free survival analysis. RESULTS 62% (31/50) of astrocytomas and 16% (8/51) of oligodendrogliomas harboured pathogenic TP53 mutations. Pathogenic hotspot mutations in codon 273 (c.817 C>T and c.818 G>A) was prevalent in astrocytoma with 58% (18/31) of tumours with these mutations. TP53 mutation status was maintained between primary and recurrent tumours in 93% of cases. In astrocytoma, overall survival of TP53 mutant patients was longer compared to TP53 wild-type patients (p<0.01) but was not significant after adjusting for age, gender, grade and IDH1 mutation status. In contrast, astrocytoma patients with specific TP53 mutation in codon 273 showed significantly better survival compared to other TP53 mutant and TP53 wild-type patients combined (p<0.01) in our multivariate analysis. Time to first recurrence (progression-free survival) of TP53 mutant patients was significantly longer than TP53 wild-type patients (p<0.01) after adjustments were made, while TP53 mutation in codon 273 was not prognostic for progression-free survival. In oligodendroglioma patients, TP53 mutations did not significantly affect overall survival and progression-free survival. CONCLUSION In agreement with others, TP53 mutation is more prevalent in Astrocytoma and mutations in codon 273 are significantly associated with longer survival.

An Integrative Survival Analysis for Multicentric Low-Grade Glioma

2020 ◽  
Vol 134 ◽  
pp. e189-e195 ◽  
Author(s):  
Tianwei Wang ◽  
Yanping Yang ◽  
Xiaoke Xu ◽  
Xiaodong Niu ◽  
Renhao Yang ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Low Grade Glioma ◽  
Low Grade

Survival Advantage From Higher-Dose Radiation Therapy for Clinically Localized Prostate Cancer Treated on the Radiation Therapy Oncology Group Trials

2000 ◽  
Vol 18 (14) ◽  
pp. 2740-2746 ◽  
Author(s):  
Richard Valicenti ◽  
Jiandong Lu ◽  
Miljenko Pilepich ◽  
Sucha Asbell ◽  
David Grignon
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Radiation Therapy ◽  
Radiation Dose ◽  
Radiation Therapy Oncology Group ◽  
Localized Prostate Cancer ◽  
Disease Specific Survival ◽  
Oncology Group ◽  
Dose Radiation ◽  
Disease Specific

PURPOSE: We evaluated the effect of external-beam radiation therapy on disease-specific survival (death from causes related to prostate cancer) and overall survival in men with clinically localized prostate cancer. METHODS: From 1975 to 1992, 1,465 men with clinically localized prostate cancer received radiation therapy on four Radiation Therapy Oncology Group phase III randomized trials and were pooled for this analysis. No one received androgen-deprivation therapy with his initial treatment. All original histology had central pathologic review for grading using the Gleason classification system. Total delivered radiation dose ranged from 60 to 78 Gy (median, 68.4 Gy). The median follow-up time was 8 years. RESULTS: A Cox regression model revealed that Gleason score was an independent predictor of disease-specific survival and overall survival. The 10-year disease-specific survival rates by Gleason score were as follows: score of 2 through 5, 85%; score of 6, 79%; score of 7, 62%; and score of 8 through 10, 43%. Stratifying outcome by this important prognostic factor revealed that higher radiation dose was a significant predictor for improved disease-specific survival and overall survival only for those patients whose cancers had Gleason scores of 8 through 10 (P < .05). After adjusting for clinical T stage, nodal status, and age, treating with a higher radiation dose was associated with a 29% lower relative risk of death from prostate cancer and 27% reduced mortality rate (P < .05). CONCLUSION: These data demonstrate that higher-dose radiation therapy can significantly reduce the risk of dying from prostate cancer in men with clinically localized disease. This survival benefit is restricted to men with poorly differentiated cancers.

scholarly journals Six Immune Associated Genes Construct Prognostic Model Evaluate Low-Grade Glioma

2020 ◽  
Vol 11 ◽  
Author(s):  
Yin Qiu Tan ◽  
Yun Tao Li ◽  
Teng Feng Yan ◽  
Yang Xu ◽  
Bao Hui Liu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Risk Score ◽  
Survival Rates ◽  
Low Grade Glioma ◽  
The Cancer Genome Atlas ◽  
Low Grade ◽  
Sequencing Analysis ◽  
Six Genes ◽  
Genome Atlas ◽  
Overall Survival Rates

BackgroundThe immunotherapy of Glioma has always been a research hotspot. Although tumor associated microglia/macrophages (TAMs) proves to be important in glioma progression and drug resistance, our knowledge about how TAMs influence glioma remains unclear. The relationship between glioma and TAMs still needs further study.MethodsWe collected the data of TAMs in glioma from NCBI Gene Expression Omnibus (GEO) that included 20 glioma samples and 15 control samples from four datasets. Six genes were screened from the Differential Expression Gene through Gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein–protein interaction (PPI) network and single-cell sequencing analysis. A risk score was then constructed based on the six genes and patients’ overall survival rates of 669 patients from The Cancer Genome Atlas (TCGA). The efficacy of the risk score in prognosis and prediction was verified in Chinese Glioma Genome Atlas (CGGA).ResultsSix genes, including CD163, FPR3, LPAR5, P2ry12, PLAUR, SIGLEC1, that participate in signal transduction and plasma membrane were selected. Half of them, like CD163, FPR3, SIGLEC1, were mainly expression in M2 macrophages. FPR3 and SIGLEC1 were high expression genes in glioma associated with grades and IDH status. The overall survival rates of the high risk score group was significantly lower than that of the low risk score group, especially in LGG.ConclusionJoint usage of the 6 candidate genes may be an effective method to diagnose and evaluate the prognosis of glioma, especially in Low-grade glioma (LGG).

Phase II Trial of High-Dose Conformal Radiation Therapy With Concurrent Hepatic Artery Floxuridine for Unresectable Intrahepatic Malignancies

2005 ◽  
Vol 23 (34) ◽  
pp. 8739-8747 ◽  
Author(s):  
Edgar Ben-Josef ◽  
Daniel Normolle ◽  
William D. Ensminger ◽  
Suzette Walker ◽  
Daniel Tatro ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Radiation Therapy ◽  
Radiation Dose ◽  
Hepatic Artery ◽  
Median Survival ◽  
Phase Ii Trial ◽  
High Dose ◽  
Hepatobiliary Tumors ◽  
Historical Controls ◽  
Dose Radiation

Purpose A phase II trial was conducted to determine if high-dose radiation with concurrent hepatic arterial floxuridine would improve survival in patients with unresectable intrahepatic malignancies. Patients and Methods Three-dimensional conformal high-dose radiation therapy was delivered concurrently with hepatic arterial floxuridine in 128 patients. The radiation dose was based on a normal-tissue complication probability model and subjected the patient to an estimated maximum risk of radiation-induced liver disease of 10% to 15%. The study design provided more than 80% power to detect a two-fold increase in median survival compared with historical controls at a 5% significance level. Results The median radiation dose delivered was 60.75 Gy (1.5-Gy fractions bid). At a median follow-up time of 16 months (26 months in patients who were alive) the median survival was 15.8 months (95% CI, 12.6 to 18.3 months), significantly longer than in the historical control. The actuarial 3-year survival was 17%. The total dose was the only significant predictor of survival. Primary hepatobiliary tumors had a significantly greater tendency to remain confined to the liver than did colorectal cancer metastases. Overall toxicity was acceptable, with 27 patients (21%) and 11 patients (9%) developing grade 3 and 4 toxicity, respectively, and one treatment-related death. Conclusion The results suggest that, compared with historical controls, high-dose focal liver irradiation with hepatic artery floxuridine prolongs survival in patients with unresectable chemotherapy-refractory metastatic colorectal cancer and primary hepatobiliary tumors. This provides a rationale for intensification of local therapy for unresectable hepatobiliary cancers and integration of this regimen with newer systemic therapy for patients with colorectal cancer.

Sign in / Sign up

Export Citation Format

Share Document