Radiotherapy for High-Grade Gliomas

Nieder, Carsten; Andratschke, Nicolaus; Wiedenmann, Nicole; Busch, Raymonde; Grosu, Anca L.; Molls, M.

doi:10.1007/s00066-004-1220-7

Cited by 83 publications

(20 citation statements)

References 36 publications

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“…The fractionation scheme in the salvage setting has also been evaluated, where Nieder et al [26] demonstrated that altered fractionation (2 vs. 3 Fx per day) did not significantly improve survival, nor did it improve survival when looking at institutional historical controls. Also, dosage of radiation did not appear to influence survival, as a total dose of 60–70 Gy did not have any apparent benefits when compared to a total dose of 50–60 Gy.…”

Section: Discussionmentioning

confidence: 99%

Re-Irradiation with Stereotactic Radiosurgery/Radiotherapy for Recurrent High-Grade Gliomas: Improved Survival in the Modern Era

Gigliotti

Hasan

Karlovits

et al. 2018

Stereotact Funct Neurosurg

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Objective: The aim of this study was to evaluate the efficacy of stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) as salvage therapy for recurrent high-grade glioma and to look at the overall efficacy of treatment with linear accelerator (LINAC)-based radiosurgery and fractionated radiotherapy. Methods: From 2010 to 2017, a total of 25 patients aged 23–74 years were re-irradiated with LINAC-based SRS and fSRT. Patients were treated to a median dose of 25 Gy in 5 fractions. Results: The median overall survival (OS) after (initial) diagnosis was 39 months with an actuarial 1-, 3-, and 5-year OS rate of 88, 56, and 30%, respectively. After treatment with SRS or fSRT, the median OS was 9 months with an actuarial 1-year OS rate of 29%. Local control, assessed for 28 tumors, after 6 months was 57%, while local control after 1 year was 39%. Three patients experienced local failure. There was no evidence of toxicity noted after SRS or fSRT throughout the follow-up period. Conclusion: SRS and fSRT remain a safe, reasonable, effective treatment option for re-irradiation following recurrent glioblastoma. Additionally, treatment volume may predict local control in the salvage setting.

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Section: Discussionmentioning

confidence: 99%

Re-Irradiation with Stereotactic Radiosurgery/Radiotherapy for Recurrent High-Grade Gliomas: Improved Survival in the Modern Era

Gigliotti

Hasan

Karlovits

et al. 2018

Stereotact Funct Neurosurg

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“…A number of strategies for modifying the delivery of RT (4–6) have been tested, without an improvement in survival. Integration of cytotoxic agents as radiation modifiers into GBM treatment protocols (7) has been disappointing.…”

Section: Introductionmentioning

confidence: 99%

A Phase 2 Study of Concurrent Radiation Therapy, Temozolomide, and the Histone Deacetylase Inhibitor Valproic Acid for Patients With Glioblastoma

Krauze

Myrehaug

Chang

et al. 2015

International Journal of Radiation Oncology*Biology*Physics

169

105

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Purpose Valproic acid (VPA) is an antiepileptic agent with histone deacetylase inhibitor (HDACi) activity shown to sensitize glioblastoma (GBM) cells to radiation in pre-clinical models. We evaluated the addition of VPA to standard radiation therapy (RT) and temozolomide (TMZ) in patients with newly diagnosed GBM. Methods and Materials Thirty-seven patients with newly diagnosed GBM were enrolled between July 2006 and April 2013. Patients received VPA, 25 mg/kg orally, divided into 2 daily doses concurrent with RT and TMZ. The first dose of VPA was given 1 week before the first day of RT at 10 to 15 mg/kg/day and subsequently increased up to 25 mg/kg/day over the week prior to radiation. VPA- and TMZ-related acute toxicities were evaluated using Common Toxicity Criteria version 3.0 (National Cancer Institute Cancer Therapy Evaluation Program) and Cancer Radiation Morbidity Scoring Scheme for toxicity and adverse event reporting (Radiation Therapy Oncology Group/European Organization for Research and Treatment). Results A total of 81% of patients took VPA according to protocol. Median overall survival (OS) was 29.6 months (range: 21–63.8 months), and median progression-free survival (PFS) was 10.5 months (range: 6.8–51.2 months). OS at 6, 12, and 24 months was 97%, 86%, and 56%, respectively. PFS at 6, 12, and 24 months was 70%, 43%, and 38% respectively. The most common grade 3/4 toxicities of VPA in conjunction with RT/TMZ therapy were blood and bone marrow toxicity (32%), neurological toxicity (11%), and metabolic and laboratory toxicity (8%). Younger age and class V recursive partitioning analysis results were significant for both OS and PFS. VPA levels were not correlated with grade 3/4 toxicity levels. Conclusions Addition of VPA to concurrent RT/TMZ in patients with newly diagnosed GBM was well tolerated. Additionally, VPA may result in improved outcomes compared to historical data and merits further study.

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“…Although various radiotherapy techniques and altered fractionation schedules [1-6], as well as different chemotherapeutic regimens [7,8] have been implemented, the overall survival of glioblastoma patients remains rather poor, with a median survival of 12-18 months. A major problem concerning the study of these patients is the identification of robust prognostic parameters.…”

Section: Introductionmentioning

confidence: 99%

Volumetric and MGMT parameters in glioblastoma patients: Survival analysis

et al. 2012

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BackgroundIn this study several tumor-related volumes were assessed by means of a computer-based application and a survival analysis was conducted to evaluate the prognostic significance of pre- and postoperative volumetric data in patients harboring glioblastomas. In addition, MGMT (O6-methylguanine methyltransferase) related parameters were compared with those of volumetry in order to observe possible relevance of this molecule in tumor development.MethodsWe prospectively analyzed 65 patients suffering from glioblastoma (GBM) who underwent radiotherapy with concomitant adjuvant temozolomide. For the purpose of volumetry T1 and T2-weighted magnetic resonance (MR) sequences were used, acquired both pre- and postoperatively (pre-radiochemotherapy). The volumes measured on preoperative MR images were necrosis, enhancing tumor and edema (including the tumor) and on postoperative ones, net-enhancing tumor. Age, sex, performance status (PS) and type of operation were also included in the multivariate analysis. MGMT was assessed for promoter methylation with Multiplex Ligation-dependent Probe Amplification (MLPA), for RNA expression with real time PCR, and for protein expression with immunohistochemistry in a total of 44 cases with available histologic material.ResultsIn the multivariate analysis a negative impact was shown for pre-radiochemotherapy net-enhancing tumor on the overall survival (OS) (p = 0.023) and for preoperative necrosis on progression-free survival (PFS) (p = 0.030). Furthermore, the multivariate analysis confirmed the importance of PS in PFS and OS of patients. MGMT promoter methylation was observed in 13/23 (43.5%) evaluable tumors; complete methylation was observed in 3/13 methylated tumors only. High rate of MGMT protein positivity (> 20% positive neoplastic nuclei) was inversely associated with pre-operative tumor necrosis (p = 0.021).ConclusionsOur findings implicate that volumetric parameters may have a significant role in the prognosis of GBM patients. Furthermore, volumetry could help not only to improve the prediction of outcome but also the outcome itself by identifying patients at high risk of treatment failure and, thus, seek alternative treatment for these patients. In this small series, MGMT protein was associated with less aggressive tumor characteristics.

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Radiotherapy for High-Grade Gliomas

Abstract: Altered fractionation shortens the overall treatment time for adult patients with supratentorial high-grade gliomas. However, there is no significant survival improvement.

Cited by 83 publications

References 36 publications

Re-Irradiation with Stereotactic Radiosurgery/Radiotherapy for Recurrent High-Grade Gliomas: Improved Survival in the Modern Era

Re-Irradiation with Stereotactic Radiosurgery/Radiotherapy for Recurrent High-Grade Gliomas: Improved Survival in the Modern Era

A Phase 2 Study of Concurrent Radiation Therapy, Temozolomide, and the Histone Deacetylase Inhibitor Valproic Acid for Patients With Glioblastoma

Volumetric and MGMT parameters in glioblastoma patients: Survival analysis

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