MRI evaluation of the effects of whole brain radiotherapy on breast cancer brain metastasis

Crowe, William N.; Wang, Lulu; Zhang, Zhongwei; Varagić, Jasmina; Bourland, J. Daniel; Chan, Michael D.; Habib, Amyn A.; Zhao, Dawen

doi:10.1080/09553002.2019.1554920

Cited by 24 publications

(31 citation statements)

References 34 publications

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“…5). This data is consistent with increased K trans values (BBB permeability measured clinically) seen in quantitative DCE MRI in irradiated tumors at 24hrs post-irradiation (70). Broad beam radiotherapy also displayed increased BTB permeability in treated lesions (71).…”

Section: Discussionsupporting

confidence: 83%

Radiation increases BTB permeability in a preclinical model of breast cancer brain metastasis.

Sprowls

Arsiwala

Kielkowski

et al. 2020

Preprint

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Background Brain metastasis is a devastating stage of cancer progression, occurring in ~30% of metastatic breast cancer patients. Two-year survival rates for these patients is low, and most typically survive less than one year. Treatments for these women are limited by the blood-brain barrier, but include cytotoxic chemotherapy, surgical resection, and radiation therapy (whole-brain radiotherapy or stereotactic radiosurgery). Radiotherapy is considered to be capable of inducing disruption of the blood-brain barrier and eliciting an abscopal response to extracranial tumors. Methods A combination of ionization chamber and Gafchromic film dosimetry was used to commission and determine dose outputs for our experimental design. Dose deposition in-vivo was verified by immunohistochemistry. To evaluate the effects of ionizing radiation at the normal blood-brain barrier and the blood-tumor barrier, athymic nude and FVB mice were used. Athymic nude mice were injected with MDA-MB-231Br cells. Lesions were allowed to develop for ~28 days. Mice were then irradiated at the prescribed dose. Prior to tissue collection, mice were injected with Texas red, followed by a vascular washout with physiological buffer. Fluorescence in normal and diseased brain was quantified by fluorescent microscopy. Results Using a 10mmx10mm collimator, determined to have adequate field homogeneity as determined by Gafchromic film analysis, we were able to successfully treat a single hemisphere in mice. The blood-brain-barrier remained undisrupted in athymic nude mice at doses up to 12Gy compared to untreated brain and radiation naïve controls. Immune competent FVB mice treated with radiation showed significant blood-brain barrier disruption at a dose of 12Gy only. The blood-tumor barrier showed significant disruption at 24hrs following radiation treatment (6 or 12Gy). Conclusion Our study demonstrated that radiation therapy disrupts the blood-tumor barrier, but fails to disrupt the normal blood-brain barrier in athymic nude mice. However, in FVB immune competent mice, the blood-brain barrier was disrupted at a dose of 12Gy, suggesting an abscopal-like response impacts extent of barrier leakage.

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Section: Discussionsupporting

confidence: 83%

Radiation increases BTB permeability in a preclinical model of breast cancer brain metastasis.

Sprowls

Arsiwala

Kielkowski

et al. 2020

Preprint

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“…From a biological standpoint, this finding might reflect early and subtle posttreatment vasogenic edema with weakening of the blood–brain barrier, possibly explaining the previously reported effects of radiation therapy on T 1 DN‐to‐pons ratios in patients exposed to GBCAs 13,14,21 . Indeed, a recent study based on a murine model with analysis of DWI and MRI dynamic contrast‐enhanced imaging, before and 24 hours after three daily fractions of 4 Gy whole‐brain radiotherapy, showed increased ADC values together with higher permeability (parameter K trans ) in the treated metastatic tumors 30 . Moreover, another study performed with a 9.4T MRI scanner on a murine model showed a gradual increase of the ADC values among various regions of the entire brain after irradiation 31 .…”

Section: Discussionmentioning

confidence: 93%

Effect of Exposure to Gadodiamide and Brain Irradiation on T₁‐Weighted Images and ADC Maps of the Dentate Nucleus

Mallio

Parillo

Zobel

et al. 2020

Magnetic Resonance Imaging

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Background Brain irradiation is considered a cofactor influencing the dentate nucleus (DN) signal intensity (SI) on unenhanced T1‐weighted images in patients exposed to gadolinium‐based contrast agents (GBCAs). Purpose To assess the effect of gadodiamide and whole‐brain radiation therapy (WBRT) on T1‐weighted images and on apparent diffusion coefficient (ADC) maps of DN. Study Type Single‐center retrospective. Population In all, 125 patients who underwent brain MRIs were classified into four groups: 1) patients who did neither receive intravenous GBCAs injections nor irradiation (controls); 2) patients having ≥3 GBCAs‐enhanced scans and no WBRT; 3) patients having WBRT and < 3 GBCAs‐enhanced scans; and 4) patients having WBRT and ≥ 3 GBCAs‐enhanced scans. Field Strength/Sequence 1.5T magnet, echo‐planar diffusion weighted imaging (DWI) and unenhanced T1‐weighted sequences. Assessment The DN‐to‐pons SI ratio on unenhanced T1‐weighted images and ADC values of the DN were calculated. Values were compared between groups and relative to the cumulative gadolinium dose and to the time delay after WBRT. Statistical Tests Statistical analysis included the Mann−Whitney U‐test and Spearman's rank‐order correlation. Results DN ADC values were not significantly different (P = 0.34) between patients exposed to gadodiamide (0.81 ± 0.06) and controls (0.83 ± 0.07). There were no differences in DN ADC values (P = 0.28) and DN‐to‐pons SI ratios (P = 0.42) between patients exposed to WBRT (ADC values: 0.85 ± 0.09; SI ratio: 1.11 ± 0.10) and controls (ADC values: 0.83 ± 0.06; SI ratio: 1.09 ± 0.06). There was a significant negative correlation between DN ADC values and the time (days) since the end of WBRT (r = − 0.33; 95% confidence interval [CI]: −0.55, −0.06; P < 0.05). Data Conclusion We did not find changes suggestive of gadolinium‐related tissue microstructural damage of the DN. The ADC values of the DN are associated with the time from WBRT. Level of Evidence 3 Technical Efficacy Stage 5

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“…Presently, one of the main mechanisms of tumor therapy is to induce apoptosis of tumor cells through various therapeutic measures [38][39][40][41][42]. Radiotherapy is a local treatment method that uses radiation to reduce or eliminate tumor lesions and is one of the commonly used methods in clinical tumor therapy [43]. In recent years, many studies have shown that radiotherapy induces apoptosis in tumor cells [44][45][46].…”

Section: Correlation Between Mir-210 and The Efficacy Of Radiotherapy For Ovarian Cancer And Its Mechanismsmentioning

confidence: 99%

Effect of MicroRNA-210 on the Growth of Ovarian Cancer Cells and the Efficacy of Radiotherapy

Zhao

Liu

Wen

et al. 2020

Gynecol Obstet Invest

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Objective: The objective of this study is to explore the role of miR-210 in the growth of ovarian cancer cells and the correlation with radiotherapy and to elucidate underlying molecular mechanisms. Methods: Human ovarian cancer cell lines OVCAR3 and SKOV3 were cultured in vitro, and miR-210 over-expression and low-expression ovarian cancer cell models were established by cell transfection. MTT assay was used to detect the proliferation activity. Transwell was used to detect the migration and invasion abilities. Western blot measured the expression of proteins related to cell proliferation, migration, and invasion. The cells were treated with different doses of ionizing radiation, and then the cell proliferation activity was detected by MTT. The expression of apoptosis-related proteins was detected by Western blot. The Caspase-Glo® Kit was used to detect the activity of cellular caspase 3/7 enzymes. Results: The proliferation, migration, and invasion abilities of miR-210 over-expression ovarian cancer cells were increased (p < 0.05), the expressions of PTEN and E-cadherin were decreased, and the expression of p-Protein kinase B (AKT), N-cadherin, Snail, and Vimentin were elevated. After ionizing radiation, the sensitivity of miR-210 over-expression cells to radiotherapy was decreased, the expression of apoptosis-related protein Bax was decreased, the expression of Bcl-2 was increased, and the activity of cellular caspase 3/7 enzyme was reduced (p < 0.05). Conclusion: miR-210 can promote the proliferation, migration, and invasion of ovarian cancer cells by activating the AKT signaling pathway and regulating the expression of Epithelial-mesenchymal transition-related proteins. miR-210 can reduce the sensitivity of ovarian cancer cells to radiotherapy by inhibiting apoptosis, which might serve as a potential target for the treatment of ovarian tumors.

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MRI evaluation of the effects of whole brain radiotherapy on breast cancer brain metastasis

Cited by 24 publications

References 34 publications

Radiation increases BTB permeability in a preclinical model of breast cancer brain metastasis.

Radiation increases BTB permeability in a preclinical model of breast cancer brain metastasis.

Effect of Exposure to Gadodiamide and Brain Irradiation on T₁‐Weighted Images and ADC Maps of the Dentate Nucleus

Effect of MicroRNA-210 on the Growth of Ovarian Cancer Cells and the Efficacy of Radiotherapy

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MRI evaluation of the effects of whole brain radiotherapy on breast cancer brain metastasis

Cited by 24 publications

References 34 publications

Radiation increases BTB permeability in a preclinical model of breast cancer brain metastasis.

Radiation increases BTB permeability in a preclinical model of breast cancer brain metastasis.

Effect of Exposure to Gadodiamide and Brain Irradiation on T1‐Weighted Images and ADC Maps of the Dentate Nucleus

Effect of MicroRNA-210 on the Growth of Ovarian Cancer Cells and the Efficacy of Radiotherapy

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Effect of Exposure to Gadodiamide and Brain Irradiation on T₁‐Weighted Images and ADC Maps of the Dentate Nucleus