Use of Magnetic Resonance Imaging to Assess Blood-Brain/Blood-Glioma Barrier Opening During Conformal Radiotherapy

Cao, Yue; Tsien, Christina; Shen, Zhongxiang; Tatro, Daniel; Haken, Randall K. Ten; Kessler, Marc L.; Chenevert, Thomas L.; Lawrence, Theodore S.

doi:10.1200/jco.2005.07.144

Cited by 145 publications

(113 citation statements)

References 20 publications

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“…Radiation therapy has been shown to increase permeability in the blood-brain barrier. 5 The enhanced permeability of BRAF inhibitors by radiation can increase radiosensitivity and may improve local control. When BRAF inhibitor therapy was given before SRS, we did not find an association with local control; however, this may solely be a result of the relatively small number of patients who received BRAF inhibitor therapy in that setting.…”

Section: Discussionmentioning

confidence: 99%

Local control after stereotactic radiosurgery for brain metastases in patients with melanoma with and without BRAF mutation and treatment

Ly¹,

Bagshaw²,

Anker

et al. 2015

JNS

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OBJECT BRAF inhibitors improve progression-free and overall survival in patients with metastatic melanoma. Brain metastases are common, and stereotactic radiosurgery (SRS) has been used, resulting in excellent local control. Because BRAF inhibitors are associated with intracranial responses, the authors hypothesized that BRAF inhibitors would improve local control in patients with melanoma who are receiving SRS for brain metastases. METHODS The authors retrospectively identified patients with metastatic melanoma who had been tested for BRAF mutation and treated with SRS for brain metastases. Patients with previous resection, multiple brain metastases, or multiple courses of SRS were eligible. SRS was delivered in a single fraction to a median dose of 2000 cGy. Patients with a BRAF mutation were treated with a BRAF inhibitor on the basis of physician preference. RESULTS The authors identified 52 patients who were treated in 82 treatment sessions for 185 brain metastases and 13 tumor beds. At a median follow-up of 10.5 months, the 1-year local control rate was 69.2%. At 1 year, the local control rate for brain metastases in patients with BRAF mutation with BRAF treatment was 85.0%, and the local control rate for brain metastases in those without BRAF treatment was 51.5% (p = 0.0077). The rates of distant brain failure, freedom from whole-brain radiation, and overall survival were not different on the basis of BRAF mutation status or inhibitor therapy. The number of new intratumoral hemorrhages after SRS was increased significantly in patients with BRAF treatment. CONCLUSIONS Treatment with BRAF inhibitors was associated with improved local control after SRS in patients with melanoma and brain metastases. An increased number of intratumoral hemorrhages was associated with BRAF inhibitor therapy.

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Section: Discussionmentioning

confidence: 99%

Local control after stereotactic radiosurgery for brain metastases in patients with melanoma with and without BRAF mutation and treatment

Ly¹,

Bagshaw²,

Anker

et al. 2015

JNS

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“…EGFR has been associated with high malignant degree and poor outcomes in malignant gliomas. The BBB prevents certain chemotherapy drugs and large molecular substances from penetrating the brain tissue, and surgery, radiotherapy and the tumor itself disrupt BBB integrity (29)(30)(31). Radioimmunoscintigraphy with 99mTc-labelled nimotuzumab exhibits a high sensitivity, specificity and accuracy in in vivo detection of gliomas in patients (32).…”

Section: Discussionmentioning

confidence: 99%

Nimotuzumab prolongs survival in patients with malignant gliomas: A phase I/II clinical study of concomitant radiochemotherapy with or without nimotuzumab

Hong

Peng

Liao

et al. 2012

Experimental and Therapeutic Medicine

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Abstract. The present study aimed to determine whether nimotuzumab enhances the effect of radiochemotherapy in malignant gliomas. Patients (n=41) with malignant gliomas were divided into 20 cases (treatment group) in which nimotuzumab plus radiochemotherapy were offered and 21 cases (control group) in which placebo and radiochemotherapy were administered to the patients. The response to treatment was evaluated according to the Response Evaluation Criteria in Solid Tumors, the Kaplan-Meier method was used to calculate the mean and median survival times and 1-year survival rate, and the log-rank test and the Chi-square test were used to analyze the difference in the survival and response rate between the treatment and control groups. The mean survival times of the treatment and control groups were 14.3 and 10.4 months and the median survival times of the treatment and control groups were 16.5 and 10.5 months, respectively. The 1-year survival rates of the treatment and control groups were 81.3 and 69.1%, respectively, with no significant difference (P>0.05). The objective response rates of the treatment and control groups were 70.0 and 52.4%, respectively, with no significant difference (P>0.05). In conclusion, there was a trend towards improved treatment efficacy of radiochemotherapy combined with nimotuzumab against malignant gliomas. This study demonstrated that the use of nimotuzumab combined with radiotherapy and concomitant temozolomide chemotherapy is effective for malignant gliomas.

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“…The timing of bevacizumab administration in the RTOG 0825 study is also concerning. In 2005, Cao et al 49 showed that in nonenhancing tumor regions, the uptake of GBCA peaks between week 3 of radiochemotherapy and 1 month following the start of radiochemotherapy. This time period denotes the most significant BBB disruption and likely the most significant delivery of temozolomide.…”

Section: The Future Of Bevacizumab In Up-frontmentioning

confidence: 99%

The paradoxical effect of bevacizumab in the therapy of malignant gliomas

2011

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One rationale behind the use of agents that inhibit vascular endothelial growth factor in the therapy of primary CNS malignancies is based upon the concept that normalization of tumor vasculature with a decrease in tumor interstitial pressure will improve access of cytoreductive drugs and improve radiotherapy efficacy due to increased oxygen delivery. However, several studies have raised the concern that these agents may both rapidly restore the low permeability characteristics of the blood-brain barrier and counteract the beneficial effect of pseudoprogression. The result may be decreased therapeutic efficacy while increasing infiltration by co-opting normal vessels. In this discussion, we examine both histologic and radiographic tumor progression in the context of antiangiogenic agents. Issues dealing with the safety of bevacizumab (Avastin ® , Genentech, South San Francisco, CA) and its potential to decrease efficacy of standard radiochemotherapy when used to treat patients with newly diagnosed malignant glioma are emphasized. Bevacizumab is a recombinant humanized monoclonal immunoglobulin G (IgG)1 antibody that binds to vascular endothelial growth factor (VEGF) and prevents the proliferation of endothelial cells and formation of new blood vessels. 1 VEGF has a role in endothelial cell survival, proliferation, invasion, and migration, which all affect tumor progression and angiogenesis.2 Treatment with bevacizumab was quickly implemented for salvage therapy in progressive malignant gliomas after its efficacy was demonstrated in metastatic colon cancer 3 and in non-small-cell lung cancer. 4 Multiple groups using bevacizumab plus chemotherapy 2,5-12 and 2 phase II trials using bevacizumab alone 13,14 have demonstrated impressive imaging responses with increased overall survival (OS) and progression-free survival (PFS) in recurrent glioma patients relative to historical data in patients who received chemotherapy alone. 15,16 The results of the phase II trials were so compelling that in May 2009, the US Food and Drug Administration granted approval for the use of bevacizumab for the second-line treatment of glioblastoma multiforme (GBM).17 Additionally, 2 recent phase II trials explored the use of bevacizumab plus chemotherapy as initial therapy for newly diagnosed GBM 18,19 and several other centers are enrolling patients in 2 large phase III trials of temozolomide and radiation with and without bevacizumab for the treatment of newly diagnosed GBM. 20,21VESSEL NORMALIZATION The general rationale behind using bevacizumab in combination with chemotherapy for malignant gliomas is twofold. First, bevacizumab normalizes vessels in the CNS by a mechanism similar to that of solid tumors outside the CNS. Bevacizumab decreases the abnormal morphology and organization of tumor-related vasculature that causes inefficient transport of oxygen and therapeutic drugs to

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Use of Magnetic Resonance Imaging to Assess Blood-Brain/Blood-Glioma Barrier Opening During Conformal Radiotherapy

Cited by 145 publications

References 20 publications

Local control after stereotactic radiosurgery for brain metastases in patients with melanoma with and without BRAF mutation and treatment

Local control after stereotactic radiosurgery for brain metastases in patients with melanoma with and without BRAF mutation and treatment

Nimotuzumab prolongs survival in patients with malignant gliomas: A phase I/II clinical study of concomitant radiochemotherapy with or without nimotuzumab

The paradoxical effect of bevacizumab in the therapy of malignant gliomas

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