scholarly journals Outcomes After Proton Therapy Reirradiation for Malignant Glioma: Prospective Analysis of Over 100 Patients from the Proton Collaborative Group

2021 ◽  
Author(s):  
Robert H Press ◽  
Shaakir Hasan ◽  
J Isabelle Choi ◽  
Arpit M Chhabra ◽  
Lia M Halasz ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Proton Therapy ◽  
Proportional Hazards ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Collaborative Group ◽  
Time Interval ◽  
Who Grade ◽  
Who Grade Iii ◽  
Grade Iii

Abstract Purpose: The optimal salvage treatment for malignant glioma after prior radiotherapy (RT) is not well established. Proton therapy (PT) is an attractive treatment modality for reirradiation (ReRT) of recurrent disease; however, data are limited.Methods: The prospective, multi-institutional Proton Collaborative Group (PCG) registry was queried for patients with malignant glioma who previously received RT and underwent PT-ReRT between 7/2011-10/2018. Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method and Cox proportional hazards regression analysis. Results: 109 consecutive patients were identified. Median follow-up was 11.2 months and median time interval (TI) from prior RT (median 59.3 Gy) to PT-ReRT (median 49.6 Gy) was 45.7 months. Primary histology was glioblastoma (n=62), oligodendroglioma (n=26), and astrocytoma (n=20). Median PFS and OS was 6.1 and 11.1 months, respectively. On UVA, improved PFS was associated with oligodendroglioma (HR 0.39) and astrocytoma (HR 0.55) histologies, WHO Grade III (HR 0.36), TI (HR 0.989), surgical resection (HR 0.39), and PT-ReRT dose ≥50 Gy (HR 0.59) (all p<0.03), while improved OS was associated with oligodendroglioma histology (HR 0.35), WHO grade III (HR 0.33), ECOG 0 (HR 0.47), TI (HR 0.985), and PT-ReRT dose ≥50 Gy (HR 0.58) (all p<0.04). Late Grade 3 toxicities occurred in 5.6% of patients with no attributable acute or late Grade 4-5 events.Conclusion: In the largest series of glioma PT-ReRT reported to date, retreatment appears well tolerated with acceptable outcomes and favorable toxicities compared to photon historical controls. Dose escalation achievable with PT may improve outcomes for well-selected patients.

scholarly journals QOLP-05. OLANZAPINE FOR REFRACTORY CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING IN MALIGNANT GLIOMA PATIENTS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii175-ii175
Author(s):  
Mallika Patel ◽  
Katherine Peters ◽  
Eric Lipp ◽  
Justin Low ◽  
James Herndon ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Large Scale ◽  
Chart Review ◽  
Mgmt Promoter Methylation ◽  
Emetogenic Chemotherapy ◽  
Nausea And Vomiting ◽  
Highly Emetogenic Chemotherapy ◽  
Who Grade ◽  
Who Grade Iii ◽  
Grade Iii

Abstract INTRODUCTION Malignant glioma (MG) patients often experience chemotherapy-induced nausea and vomiting (CINV). Olanzapine has recently been added to national anti-emesis guidelines for patients on moderately/highly emetogenic chemotherapy. In this retrospective study, we investigated the use of olanzapine for refractory-CINV (R-CINV) in MG patients. METHODS In this chart review, we queried adult MG patients with KPS ≥ 70 who received olanzapine from January 2019-March 2020. Patients were included if they were prescribed olanzapine for CINV. Data on nausea/vomiting improvement, olanzapine dosing/schedule, number of refractory anti-emetic trials, concomitant corticosteroid use, and demographics were collected. RESULTS We identified 21 MG patients who were prescribed olanzapine, with 9 of those patients receiving olanzapine specifically for CINV. Seven patients had WHO grade IV glioma, and 2 patients had anaplastic astrocytoma (WHO grade III). Five of 9 patients (55.6%) were male, all were Caucasian and median age was 54 years. Patients tried an average of 3 anti-emetics prior to initiating olanzapine for R-CINV. Only one patient was taking concomitant corticosteroids; which is not in concordance with national anti-emesis guidelines. Four of 9 patients (44.4%) achieved control of R-CINV with olanzapine. The olanzapine dose and key biomarkers (IDH-status, MGMT promoter methylation) were similar between those experiencing R-CINV and those without symptoms. CONCLUSIONS In this study, we find that approximately half of patients with R-CINV achieved improved nausea and vomiting control with the addition of olanzapine. The lack of corticosteroid use for anti-emesis in MG continues to make this population challenging to manage. The relatively high success rate in patients that had failed, on average, 3 anti-emetics, suggests that olanzapine may be a potent addition to the anti-emetic toolkit for MG patients. These results inspire further large-scale research to validate this observation and define the optimal role for olanzapine in treating R-CINV in MG patients.

scholarly journals A molecularly integrated grade for meningioma

2021 ◽  
Author(s):  
Joseph Driver ◽  
Samantha E Hoffman ◽  
Sherwin Tavakol ◽  
Eleanor Woodward ◽  
Eduardo A Maury ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Clinical Care ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
World Health ◽  
Brier Score ◽  
Gradient Boosting ◽  
Grading System ◽  
Prognostic Information ◽  
Who Grade

Abstract Background Meningiomas are the most common primary intracranial tumor in adults. Clinical care is currently guided by the World Health Organization (WHO) grade assigned to meningiomas, a 3-tiered grading system based on histopathology features, as well as extent of surgical resection. Clinical behavior, however, often fails to conform to the WHO grade. Additional prognostic information is needed to optimize patient management. Methods We evaluated whether chromosomal copy-number data improved prediction of time-to-recurrence for patients with meningioma who were treated with surgery, relative to the WHO schema. The models were developed using Cox proportional hazards, random survival forest, and gradient boosting in a discovery cohort of 527 meningioma patients and validated in 2 independent cohorts of 172 meningioma patients characterized by orthogonal genomic platforms. Results We developed a 3-tiered grading scheme (Integrated Grades 1-3), which incorporated mitotic count and loss of chromosome 1p, 3p, 4, 6, 10, 14q, 18, 19, or CDKN2A. 32% of meningiomas reclassified to either a lower-risk or higher-risk Integrated Grade compared to their assigned WHO grade. The Integrated Grade more accurately identified meningioma patients at risk for recurrence, relative to the WHO grade, as determined by time-dependent area under the curve, average precision, and the Brier score. Conclusion We propose a molecularly integrated grading scheme for meningiomas that significantly improves upon the current WHO grading system in prediction of progression-free survival. This framework can be broadly adopted by clinicians with relative ease using widely available genomic technologies and presents an advance in the care of meningioma patients.

scholarly journals Mitotic and Proliferative Indices in WHO Grade III Meningioma

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3351
Author(s):  
Andrea Daniela Maier ◽  
Christian Beltoft Brøchner ◽  
Jiri Bartek Jr. ◽  
Frank Eriksson ◽  
Heidi Ugleholdt ◽  
...  
Keyword(s):  
Mitotic Index ◽  
Hot Spot ◽  
Progression Free Survival ◽  
Ki 67 ◽  
Who Grade ◽  
Free Survival ◽  
Phosphohistone H3 ◽  
Proliferative Indices ◽  
Who Grade Iii ◽  
Grade Iii

Meningiomas with inherently high mitotic indices and poor prognosis, such as WHO grade III meningiomas, have not been investigated separately to establish interchangeability between conventional mitotic index counted on H&E stained slides (MI) and mitotic index counted on phosphohistone-H3 stained slides (PHH3 MI). This study investigates the agreement of MI and PHH3 MI and to analyze the association of progression-free survival (PFS) and MI, PHH3 MI, and the proliferative index (PI, Ki-67) in WHO grade III meningioma. Tumor specimens from 24 consecutive patients were analyzed for expression of Ki-67, PHH3 MI, and MI. Quantification was performed independently by two observers who made replicate counts in hot spots and overall tumor staining. Repeatability in replicate counts from MI and PHH3 MI was low in both observers. Consequently, we could not report the agreement. MI, PHH3 MI and hot spot counts of Ki-67 were associated with PFS (MI hot spot HR = 1.61, 95% CI 1.12–2.31, p = 0.010; PHH3 MI hot spot HR = 1.59, 95% CI 1.15–2.21, p = 0.006; Ki-67 hot spot HR = 1.06, 95% CI 1.02–1.11. p = 0.004). We found markedly low repeatability of manually counted MI and PHH3 MI in WHO grade III meningioma, and we could not conclude that the two methods agreed. Subsequently, quantification with better repeatability should be sought. All three biomarkers were associated with PFS.

scholarly journals ACTR-41. A PHASE II, SINGLE ARM STUDY OF OPTUNE® IN BEVACIZUMAB-NAIVE SUBJECTS WITH RECURRENT WHO GRADE III MALIGNANT GLIOMA

2016 ◽  
Vol 18 (suppl_6) ◽  
pp. vi11-vi11
Author(s):  
Daniel O’Connell ◽  
Jose Carrillo ◽  
Xiao-Tang Kong ◽  
Beverly Fu ◽  
Daniela Bota
Keyword(s):  
Malignant Glioma ◽  
Phase Ii ◽  
Who Grade ◽  
Who Grade Iii ◽  
Grade Iii

Front-Line Treatment of Low-Grade Non-Follicular Non-Hodgkin Lymphoma (Final Report of Gisl LL02 Trial).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2332-2332
Author(s):  
Maria Goldaniga ◽  
Francesco Merli ◽  
Caterina Stelitano ◽  
Vincenzo Callea ◽  
Fiorella Ilariucci ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Final Report ◽  
Low Grade ◽  
Who Grade ◽  
Free Survival ◽  
Non Hodgkin Lymphoma ◽  
Who Grade Iii ◽  
Grade Iii

Abstract Indolent Non-follicular non-Hodgkin Lymphoma (NFo-NHL) is a group of relatively frequent lymphoproliferative diseases, nevertheless extended clinical and prognostic studies are still lacking. In 2002 the Gruppo Italiano Studio Linfomi (GISL) initiated a LL02 prospective multicenter phase II trial, with the aim to evaluate the efficacy and safety of FC combination in the first-line therapy of NFo-NHL patients younger than 70 years. Between July 2002 and September 2006, 58 adult patients (35 males and 23 females, median age 64 yrs, range 40–75) affected by NFo-NHL in active disease phase, were consecutively enrolled in 12 GISL Hematological Centres. Patients were treated with a dose of 25 mg/mq Fludarabine plus 250 mg/mq Cyclophosphamide administred intravenously daily for 3 days; each cycle was repeated every 28 days for 6 courses. During the treatment patients received oral thrimethoprim-sulphametoxazole prophylaxis. After the intermediate evaluation, 48/58 patients (82.8%) had an objective response (ORR) with a 20.7% of complete remission (CR) plus 62.1% of partial remission (PR); at the final evaluation the ORR percentage was 84.5% with a 41.4% of CR (24 pts) and 43.1% of PR (25 pts); three patients were in progressive disease (5.2%) and one in stable disease (1.7%). The median overall survival (OS) was not reached with an 88% and 84% at 12 and 24 months; the progression free survival (PFS) was 89% and 77% and the event free survival (EFS) was 81% and 66% at 12 and 24 months respectively.About the toxicity profile, the major toxicity was hematological with a 18% cases of WHO grade III or IV anemia, 40% leucopenia, 33% neutropenia and 10% piastrinopenia. The 12% of patients had an infective episode wich a 7.7% of WHO grade III–IV.In conclusion the FC chemotherapy is a useful chance for advanced untreated non follicular low-grade NHL, with an optimal ORR, CR and PFS. The crucial point of FC remains OS, that not seems to be significantly improved in comparison with fludarabine alone or with standard therapy, even though the better quality of responses; Rituximab plus FC association is growing in literature as the probably key to find a real improvement also in this aspect.

scholarly journals COT-01 SYMPTOMATIC EPILEPSY INDUCED BY MALIGNANT BRAIN TUMOR

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii40-ii41
Author(s):  
Hirofumi Oyama
Keyword(s):  
Brain Tumor ◽  
Germ Cell ◽  
Malignant Glioma ◽  
Cell Tumor ◽  
Malignant Brain Tumor ◽  
Initial Symptom ◽  
Who Grade ◽  
Symptomatic Epilepsy ◽  
Who Grade Iii ◽  
Grade Iii

Abstract CASES We report about 41 cases of malignant brain tumor which were treated with operation, irradiation, chemotherapy during past 62 months. 34 cases of glioblastoma, 2 cases of malignant glioma(WHO grade III), 2 cases of medulloblastoma, 1 case of germ cell tumor, 1 case of malignant neurocytoma, and 1 case of malignant ependymoma were included in 41 cases. Two cases of glioblastoma survived over than 25 years, but the median survival of dead 11 glioblastoma cases was 22 months. 4 cases were expired among another 7 cases. RESULTS 6 cases showed mutation in ATRX and one case had mutation of IDH-1 among 34 cases of glioblastoma. One case showed mutation in ATRX and IDH-1 among 2 cases of malignant glioma. But the mutation in ATRX and IDH-1 had no correlation with convulsion. The initial symptom was epilepsy in 3 cases of glioblastoma and another 3 cases of glioblastoma showed convulsive seizure thereafter. One case of glioblastoma showed rapid aggravation of symptom after convulsion. The initial symptom was epilepsy in 1 case of malignant glioma. One case of malignant ependymoma and one case of medulloblastoma showed rapid aggravation of symptom after convulsion. DISCUSSION Nine cases showed convulsion among our 41 cases. Convulsion happened as initial symptom in 4 cases but it happened during treatment in 5 cases. Three cases among these 5 cases showed rapid aggravation of symptom after convulsion. So pre- and post-operative anti-epileptic treatment seems to be necessary.

scholarly journals Postoperative Concurrent Chemoradiotherapy Plus Apatinib for First-line Treatment of Patients with Malignant Glioma: From One Single Research Institute

2021 ◽  
Author(s):  
Zhichao FU ◽  
Xiaoyan Li ◽  
Wenmin YING ◽  
lvjuan CAI ◽  
Guo LI ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Concurrent Chemoradiotherapy ◽  
Proportional Hazards ◽  
Statistical Significance ◽  
Group Versus ◽  
Progression Free Survival ◽  
Tumor Grade ◽  
Cox Proportional Hazards ◽  
Control Group ◽  
Retrospective Case

Abstract Objective: To explore the effectiveness and safety of apatinib in patients with malignant glioma. Methods: This is a retrospective case-control study in a single center. Patients with new postoperative pathological diagnosis of malignant glioma (WHO Ⅲ~Ⅳ) were selected. Enrolled patients received concurrent chemoradiotherapy (60Gy/30f/6w; TMZ75mg/m2,po,d1-d42)combined with or without apatinib (250mg, po, d1-d42,qd), then maintain 6 cycles(28 days a cycle)of TMZ chemotherapy(200mg/m2, d1-d5) .The primary endpoints were progression free survival (PFS) and the grade of peritumoral brain edema (PTBE) evaluated by edema index(EI). The secondary endpoint was overall survival(OS). Hazard ratios of PFS and OS were compared between trials in a Cox proportional hazards model.Results: 48 patients (24 in apatinib group and 24 in control group) were enrolled in this study. The results elucidated that the mPFS of the apatinib group was longer than control group, but the difference was not statistically significant(9.63 vs. 7.33 months; P=0.073).As for mOS, the results of two groups were almost similar.(15.47 vs. 14.70 months, P=0.612). Cox multivariate regression model revealed that Apatinib was not a prognostic factor for PFS and OS (P>0.05). Multivariate analysis showed that tumor grade was an important risk factor for PFS and OS.The grade of PTBE was improved in 15 of 23 patients (65.2%) in apatinib group versus 6 of 24 (25%) in control group. There was no grade 3 or 4 adverse events and serious adverse events.Conclusion: Apatinib group can improve mPFS by 2.3 months in patients with malignant glioma,but there was no statistical significance (P>0.05).The results also indicated that apatinib conferred a significant beneficial effect on PTBE improvement. All occurred adverse reactions were moderate and controllable.

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