External Beam Radiotherapy of Recurrent Glioma: Radiation Tolerance of the Human Brain

Sminia, Peter; Mayer, Ramona

doi:10.3390/cancers4020379

Cited by 61 publications

(50 citation statements)

References 51 publications

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“…In a recent survey on re-irradiation of recurrent glioma, radiation-induced necrosis occurred with conventional fractionation beyond a cumulative EQD2 of around 100 Gy (EQD2 = equivalent total dose when applied in 2-Gy fractions, estimated using the linear quadratic model). 32 The radiation dose that can be tolerated increases with higher conformality (fractionated stereotactic radiotherapy) and smaller treatment volumes (linear accelerator [LINAC]-based stereotactic radiosurgery). 6,32 In summary, repeated injections at similar or even higher cumulative doses appear to be associated with less hematological and neurological adverse events than a single high-dose application.…”

Section: Adverse Events and Toxicitymentioning

confidence: 99%

“…32 The radiation dose that can be tolerated increases with higher conformality (fractionated stereotactic radiotherapy) and smaller treatment volumes (linear accelerator [LINAC]-based stereotactic radiosurgery). 6,32 In summary, repeated injections at similar or even higher cumulative doses appear to be associated with less hematological and neurological adverse events than a single high-dose application. This underlines the importance of biological repair mechanisms of brain tissue between the cycles.…”

Section: Adverse Events and Toxicitymentioning

confidence: 99%

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Long-term outcome of patients with WHO Grade III and IV gliomas treated by fractionated intracavitary radioimmunotherapy

Hj¹,

Poepperl²,

Goetz³

et al. 2015

JNS

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abbreviatioNs AA = anaplastic astrocytoma; ALA = 5-aminolevulinic acid; CTC = Common Toxicity Criteria; GBM = glioblastoma multiforme; HR = hazard ratio; IDH1 = isocitrate dehydrogenase; KPS = Karnofsky Performance Scale; mAB = monoclonal antibody; MGMT = O 6 -methylguanine-DNA methyltransferase; OS = overall survival; RC = resection cavity; RIT = radioimmunotherapy; RPA = recursive partitioning analysis; RTOG = Radiation Therapy Oncology Group. submitted September 16, 2014. accepted December 12, 2014. iNclude wheN citiNg Published online July 3, 2015; DOI: 10.3171/2014.12.JNS142168. disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. This work was supported by grants from the German research foundation DFG (GO998/1-1), the Deutsche Krebshilfe (10-1782-GO2), and a fund of the MMW Foundation (Verein zur Förder-ung von Wissenschaft und Forschung an der Medizinischen Fakultät der LMU München e.V.). * Drs. Reulen and Poepperl contributed equally to this work. results Median OS of patients with AA was 77.2 months (95% CI 30.8 to > 120). Five AA patients (33%) are currently alive, with a median observation time of 162.2 months. Median OS of all 40 patients with GBM was 18.9 months (95% CI 15.8-25.3), and median OS was 25.3 months (95% CI 18-30) for those patients treated with the 131 I-mAB. Three GBM patients are currently alive. One-, 2-, and 3-year survival probabilities were 100%, 93.3%, and 66.7%, respectively, for AA patients and 82.5%, 42.5%, and 15.9%, respectively, for GBM patients. Restratification of GBM patients by recursive partitioning analysis (RPA) Classes III, IV, and V produced median OSs of 31.1, 18.9, and 14.5 months, respectively (p = 0.004), which was higher than expected. Multivariate analysis confirmed the role of RPA class, age, and treatment in predicting survival. No Grade 3 or 4 hematological, nephrologic, or hepatic toxic effects were observed; 4 patients developed Grade 3 neurological deficits. Radiological signs of radionecrosis were observed in 6 patients, who were all responding well to steroids. coNclusioNs Median OS of GBM and AA patients treated with 131 I-mABs reached 25.3 and 77.2 months, respectively, thus markedly exceeding that of historical controls. Adverse events remained well controllable with the fractionated dosage regimen. Long

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Section: Adverse Events and Toxicitymentioning

confidence: 99%

Section: Adverse Events and Toxicitymentioning

confidence: 99%

Long-term outcome of patients with WHO Grade III and IV gliomas treated by fractionated intracavitary radioimmunotherapy

Hj¹,

Poepperl²,

Goetz³

et al. 2015

JNS

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“…However, in 2 overviews from reirradiation studies, no effect was noticed with respect to the time interval between the initial and reirradiation exposure. 2,3 The main limitations of our study are the following: (a) Small sample size, although series of reirradiation in patients with AG are generally small. (b) O-6-methylguanine-DNA-methyltransferase status was not assessed.…”

Section: Spinal Cord Stimulation During Reirradiation and Chemotherapymentioning

confidence: 99%

“…However, many of the aforementioned studies had included a high percentage of patients with previous complete tumor resection after relapse, and reirradiation using stereotactic radiosurgery, or hypofractionated SRT, applied to smaller tumor volumes. 2,3 Using color Doppler measurements, transcranial Doppler, and SPECT studies, we had described that SCS can increase blood flow in common carotid arteries, middle cerebral arteries, and brain tumor tissue. 5 Using the polarographic probe technique to directly measure brain tissue pO 2 we had also described that SCS can increase tumor oxygenation and decrease tumor hypoxia.…”

Section: Spinal Cord Stimulation During Reirradiation and Chemotherapymentioning

confidence: 99%

Spinal Cord Stimulation as Adjuvant During Chemotherapy and Reirradiation Treatment of Recurrent High-Grade Gliomas

et al. 2014

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Aims. Relapsed high-grade gliomas (HGGs) have poor prognoses and there is no standard treatment. HGGs have ischemia/ hypoxia associated and, as such, drugs and oxygen have low access, with increased resistance to chemotherapy and radiotherapy. Tumor hypoxia modification can improve outcomes and overall survival in some patients with these tumors. In previous works, we have described that cervical spinal cord stimulation can modify tumor microenvironment in HGG by increasing tumor blood flow, oxygenation, and metabolism. The aim of this current, preliminary, nonrandomized, study was to assess the clinical effect of spinal cord stimulation during brain reirradiation and chemotherapy deployed for the treatment of recurrent HGG; the hypothesis being that an improvement in oxygenated blood supply would facilitate enhanced delivery of the scheduled therapy. Materials and methods. Seven patients had spinal cord stimulation applied during the scheduled reirradiation and chemotherapy for the treatment of recurrent HGG (6 anaplastic gliomas and 1 glioblastoma). Median dose of previous irradiation was 60 Gy (range = 56-72 Gy) and median dose of reirradiation was 46 Gy (range = 40-46 Gy). Primary end point of the study was overall survival (OS) following confirmation of HGG relapse. Results. From the time of diagnosis of last tumor relapse before reirradiation, median OS was 39 months (95% CI = 0-93) for the overall study group: 39 months (95% CI = 9-69) for those with anaplastic gliomas and 16 months for the patient with glioblastoma. Posttreatment, doses of corticosteroids was significantly decreased (P = .026) and performance status significantly improved (P = .046). Conclusions. Spinal cord stimulation during reirradiation and chemotherapy is feasible and well tolerated. In our study, spinal cord stimulation was associated with clinical improvement and longer survival than previously reported in recurrent anaplastic gliomas. Spinal cord stimulation as adjuvant during chemotherapy and reirradiation in relapsed HGGs merits further research.

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“…Available animal data come mainly from studies investigating spinal cord tolerance to irradiation (23,24). The pathogenesis of radiation toxicity and recovery potential in the brain is assumed to be similar to the spinal cord and the structures of the CNS are assumed to have a low α/β ratio (25).…”

Section: The Biology Of Late Central Nervous System (Cns) Toxicitymentioning

confidence: 99%

Re-irradiation for Recurrent Primary Brain Tumors

Nieder

Andratschke

Grosu

2016

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Abstract. Background: Historically, radiation oncologists have been cautious about re-irradiating brain tumors because of concerns about the risks of late central nervous system (CNS) toxicity, especially radionecrosis, that may occur several months to years following treatment. Today there are still limited prospective data addressing this approach. Materials and Methods: Systematic review of published trials reporting clinical results after re-irradiation of patients with different types of brain tumors was performed. Results: Data mainly related to glioblastoma, anaplastic glioma, medulloblastoma, ependymoma and meningioma have been published. Randomized studies are scarce. As in first-line scenarios, efficacy of radiotherapy is influenced by histology. Based on the reported outcomes, preliminary recommendations for dose/fractionation regimens can be given. Conclusion: Re-irradiation of brain tumors is increasingly considered as our understanding of brain tolerance to radiation evolves and developments in radiation technology and imaging make highly accurate targeting of recurrent tumors possible. With developments in systemic therapy, further exploration of the role of re-irradiation on its own or in combination with novel agents is needed.The current postoperative standard treatment for glioblastoma (GBM) is radiotherapy with concurrent and adjuvant temozolomide. With this approach, 5-year overall survival is 9.8% compared to 1.9% with radiotherapy alone (1). Recent data suggest that maintenance therapy with tumor-treating fields in addition to temozolomide improves survival (2). Efforts have been made to standardize the target volume definition (3). Nevertheless, despite an increase in survival rates, the majority of patients progress within 10-15 months. Also for anaplastic astrocytomas and low-grade gliomas, radiotherapy remains a common first-line treatment. In these tumors, the time to progression is longer but the majority ultimately also recurs. Salvage therapy is indicated in the majority of recurrent gliomas and most patients receive systemic therapy and/or surgery at relapse.Historically, many radiation oncologists have been cautious about re-irradiating brain tumors because of concerns about the risks of toxicity, e.g., radionecrosis. Reirradiation for brain tumors is now more frequently used because developments in radiation technology and imaging allow for highly accurate targeting of biologically relevant tumor volumes and, furthermore, several studies have demonstrated the feasibility of this treatment paradigm. This review summarizes radiobiological principles behind reirradiation of different types of brain tumors and discusses the current evidence from clinical studies. Overview of Treatment Options for Recurrent GliomasExternal-beam radiotherapy is an integral part of treatment of low-and high-grade gliomas. At relapse, treatment options have included further surgical resection, systemic therapy, including prospective trials of new agents, and re-irradiation. Currently, however, there is ...

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External Beam Radiotherapy of Recurrent Glioma: Radiation Tolerance of the Human Brain

Cited by 61 publications

References 51 publications

Long-term outcome of patients with WHO Grade III and IV gliomas treated by fractionated intracavitary radioimmunotherapy

Long-term outcome of patients with WHO Grade III and IV gliomas treated by fractionated intracavitary radioimmunotherapy

Spinal Cord Stimulation as Adjuvant During Chemotherapy and Reirradiation Treatment of Recurrent High-Grade Gliomas

Re-irradiation for Recurrent Primary Brain Tumors

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