Recurrent Malignant Gliomas

Kirkpatrick, John P.; Sampson, John H.

doi:10.1016/j.semradonc.2014.06.006

Cited by 48 publications

(36 citation statements)

References 99 publications

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“…81 Overall, there is a suggestion that HF-SRS and bevacizumab may improve radiation necrosis rates compared with single-fraction SRS. On the other hand, the efficacy of these regimens would also be expected to differ widely based on the calculated BED, 110 as shown in Table 2. At this time, given the heterogeneity of patient and treatment characteristics and lack of phase III data, there is insufficient evidence to support one treatment scheme over any other.…”

Section: Recurrent Gbmmentioning

confidence: 99%

The radiosurgery fractionation quandary: single fraction or hypofractionation?

et al. 2017

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Stereotactic radiosurgery (SRS), typically administered in a single session, is widely employed to safely, efficiently, and effectively treat small intracranial lesions. However, for large lesions or those in close proximity to critical structures, it can be difficult to obtain an acceptable balance of tumor control while avoiding damage to normal tissue when single-fraction SRS is utilized. Treating a lesion in 2 to 5 fractions of SRS (termed "hypofractionated SRS" [HF-SRS]) potentially provides the ability to treat a lesion with a total dose of radiation that provides both adequate tumor control and acceptable toxicity. Indeed, studies of HF-SRS in large brain metastases, vestibular schwannomas, meningiomas, and gliomas suggest that a superior balance of tumor control and toxicity is observed compared with single-fraction SRS. Nonetheless, a great deal of effort remains to understand radiobiologic mechanisms for HF-SRS driving the dose-volume response relationship for tumors and normal tissues and to utilize this fundamental knowledge and the results of clinic studies to optimize HF-SRS. In particular, the application of HF-SRS in the setting of immunomodulatory cancer therapies offers special challenges and opportunities. Key wordsbrain metastases | hypofractionated stereotactic radiosurgery | normal tissue injury | radiobiology | stereotactic radiosurgery ii39 Kirkpatrick et al. Hypofractionated SRS

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Section: Recurrent Gbmmentioning

confidence: 99%

The radiosurgery fractionation quandary: single fraction or hypofractionation?

et al. 2017

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“…Nonetheless, in almost all patients with malignant gliomas, recurrence following initial treatment, including radiotherapy, inevitably occurs and represents grim outcomes [14]. Glioma growth and progression is heavily reliable on angiogenesis [15].…”

Section: Introductionmentioning

confidence: 99%

Dying glioma cells establish a proangiogenic microenvironment through a caspase 3 dependent mechanism

Xiao

et al. 2017

Cancer Letters

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Vascular recovery or re-angiogenesis after radiotherapy plays a significant role in tumor recurrence, whereas molecular mechanisms of this process remain elusive. In this work, we found that dying glioma cells promoted post-irradiation angiogenesis through a caspase 3 dependent mechanism. Evidence in vitro and in vivo indicated that caspase 3 inhibition undermined proangiogenic effects of dying glioma cells. Proteolytic inactivation of caspase 3 in glioma cells reduced tumorigenicity. Importantly, we identified that NF-κB/COX-2/PGE2 axis acted as downstream signaling of caspase 3, mediating proangiogenic response after irradiation. Additionally, VEGF-A, regulated by caspase 3 possibly through phosphorylated eIF4E, was recognized as another downstream factor participating in the proangiogenic response. In conclusion, these data demonstrated that caspase 3 in dying glioma cells supported the proangiogenic response after irradiation by governing NF-κB/COX-2/PGE2 axis and p-eIF4E/VEGF-A signaling. While inducing caspase 3 activation has been a generally-adopted notion in cancer therapeutics, our study counterintuitively illustrated that caspase 3 activation in dying glioma cells unfavorably supported post-irradiation angiogenesis, suggesting that radiotherapy combined with caspase 3 inhibitors may be more effective strategies due to restricted post-irradiation angiogenesis.

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“…Additionally, age was a relevant criterion to guide treatment in some centres. PS and age are established prognostic factors for first-line as well as for second-line treatments [14,[32][33][34][35][36]. Recent studies set a threshold of KPS 60 % (corresponding to ECOG 2) as a prerequisite for tumour specific treatment interventions [4,5,37,38] as inferior PS is associated with increased side effects from any intervention and lowers the chance of clinical benefit [14,36,39].…”

Section: Discussionmentioning

confidence: 99%

Patterns of care in recurrent glioblastoma in Switzerland: a multicentre national approach based on diagnostic nodes

Hundsberger

Hottinger²,

Roelcke

et al. 2015

J Neurooncol

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Despite moderate improvements in outcome of glioblastoma after first-line treatment with chemoradiation recent clinical trials failed to improve the prognosis of recurrent glioblastoma. In the absence of a standard of care we aimed to investigate institutional treatment strategies to identify similarities and differences in the pattern of care for recurrent glioblastoma. We investigated re-treatment criteria and therapeutic pathways for recurrent glioblastoma of eight neuro-oncology centres in Switzerland having an established multidisciplinary tumour-board conference. Decision algorithms, differences and consensus were analysed using the objective consensus methodology. A total of 16 different treatment recommendations were identified based on combinations of eight different decision criteria. The set of criteria implemented as well as the set of treatments offered was different in each centre. For specific situations, up to 6 different treatment recommendations were provided by the eight centres. The only wide-range consensus identified was to offer best supportive care to unfit patients. A majority recommendation was identified for non-operable large early recurrence with unmethylated MGMT promoter status in the fit patients: here bevacizumab was offered. In fit patients with late recurrent non-operable MGMT promoter methylated glioblastoma temozolomide was recommended by most. No other majority recommendations were present. In the absence of strong evidence we identified few consensus recommendations in the treatment of recurrent glioblastoma. This contrasts the limited availability of single drugs and treatment modalities. Clinical situations of greatest heterogeneity may be suitable to be addressed in clinical trials and second opinion referrals are likely to yield diverging recommendations.

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Recurrent Malignant Gliomas

Cited by 48 publications

References 99 publications

The radiosurgery fractionation quandary: single fraction or hypofractionation?

The radiosurgery fractionation quandary: single fraction or hypofractionation?

Dying glioma cells establish a proangiogenic microenvironment through a caspase 3 dependent mechanism

Patterns of care in recurrent glioblastoma in Switzerland: a multicentre national approach based on diagnostic nodes

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