Delayed cognitive deficits can be alleviated by calcium antagonist nimodipine by downregulation of apoptosis following whole brain radiotherapy

Abstract Background Brain-resident microglia have a distinct origin compared to macrophages in other organs. Under physiological conditions, microglia are maintained by self-renewal from the local pool, independent of hematopoietic progenitors. Pharmacological depletion of microglia during whole-brain radiotherapy prevents synaptic loss and long-term recognition memory deficits. However, the origin or repopulated cells and the mechanisms behind these protective effects are unknown. Methods CD45low/int/CD11b+ cells from naïve brains, irradiated brains, PLX5622-treated brains and PLX5622 + whole-brain radiotherapy-treated brains were FACS sorted and sequenced for transcriptomic comparisons. Bone marrow chimeras were used to trace the origin and long-term morphology of repopulated cells after PLX5622 and whole-brain radiotherapy. FACS analyses of intrinsic and exotic synaptic compartments were used to measure phagocytic activities of microglia and repopulated cells. In addition, concussive brain injuries were given to PLX5622 and brain-irradiated mice to study the potential protective functions of repopulated cells after PLX5622 + whole-brain radiotherapy. Results After a combination of whole-brain radiotherapy and microglia depletion, repopulated cells are brain-engrafted macrophages that originate from circulating monocytes. Comparisons of transcriptomes reveal that brain-engrafted macrophages have an intermediate phenotype that resembles both monocytes and embryonic microglia. In addition, brain-engrafted macrophages display reduced phagocytic activity for synaptic compartments compared to microglia from normal brains in response to a secondary concussive brain injury. Importantly, replacement of microglia by brain-engrafted macrophages spare mice from whole-brain radiotherapy-induced long-term cognitive deficits, and prevent concussive injury-induced memory loss. Conclusions Brain-engrafted macrophages prevent radiation- and concussion-induced brain injuries and cognitive deficits.

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Adjuvant Whole-Brain Radiotherapy Versus Observation After Radiosurgery or Surgical Resection of One to Three Cerebral Metastases: Results of the EORTC 22952-26001 Study

Yearbook of Neurology and Neurosurgery ◽

10.1016/j.yneu.2012.05.030 ◽

2012 ◽

Vol 2012 ◽

pp. 89-90

Author(s):

J. Uhm

Keyword(s):

Surgical Resection ◽

Whole Brain Radiotherapy ◽

Cerebral Metastases ◽

Whole Brain ◽

Brain Radiotherapy

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Use of a Head-Tilting Baseplate During Tomotherapy to Shorten the Irradiation Time and Protect the Hippocampus and Lens in Hippocampal Sparing-Whole Brain Radiotherapy

Technology in Cancer Research & Treatment ◽

10.1177/1533033820986824 ◽

2021 ◽

Vol 20 ◽

pp. 153303382098682

Author(s):

Kosei Miura ◽

Hiromasa Kurosaki ◽

Nobuko Utsumi ◽

Hideyuki Sakurai

Keyword(s):

At Risk ◽

Planning Target Volume ◽

Irradiation Time ◽

Organs At Risk ◽

Absorbed Dose ◽

Whole Brain Radiotherapy ◽

Target Volume ◽

Whole Brain ◽

Brain Radiotherapy ◽

Hippocampal Sparing

Purpose: The aim of this study is to comparatively examine the possibility of reducing the exposure dose to organs at risk, such as the hippocampus and lens, and improving the dose distribution of the planned target volume with and without the use of a head-tilting base plate in hippocampal-sparing whole-brain radiotherapy using tomotherapy. Methods: Five paired images of planned head computed tomography without and with tilt were analyzed. The hippocampus and planning target volume were contoured according to the RTOG 0933 contouring atlas protocol. The hippocampal zone to be avoided was delineated using a 5-mm margin. The prescribed radiation dose was 30 Gy in 10 fractions. The absorbed dose to planning target volume dose, absorbed dose to the organ at risk, and irradiation time were evaluated. The paired t-test was used to analyze the differences between hippocampal-sparing whole-brain radiotherapy with head tilts and without head tilts. Results: Hippocampal-sparing whole-brain radiotherapy with tilt was not superior in planning target volume doses using the homogeneity index than that without tilt; however, it showed better values, and for Dmean and D2%, the values were closer to 30 Gy. Regarding the hippocampus, dose reduction with tilt was significantly greater at Dmax, Dmean, and Dmin, whereas regarding the lens, it was significantly greater at Dmax and Dmin. The irradiation time was also predominantly shorter. Conclusion: In our study, a tilted hippocampal-sparing whole-brain radiotherapy reduced the irradiation time by >10%. Therefore, our study indicated that hippocampal-sparing whole-brain radiotherapy with tomotherapy should be performed with a tilt. The head-tilting technique might be useful during hippocampal-sparing whole-brain radiotherapy. This method could decrease the radiation exposure time, while sparing healthy organs, including the hippocampus and lens.

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A Dutch phase III randomized multicenter trial: whole brain radiotherapy vs. stereotactic radiotherapy for 4-10 brain metastases

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab021 ◽

2021 ◽

Author(s):

Dianne Hartgerink ◽

Anna Bruynzeel ◽

Danielle Eekers ◽

Ans Swinnen ◽

Coen Hurkmans ◽

...

Keyword(s):

Quality Of Life ◽

Side Effects ◽

Brain Metastases ◽

Survival Rates ◽

Whole Brain Radiotherapy ◽

Phase Iii ◽

Whole Brain ◽

Brain Radiotherapy ◽

One Year

Abstract Background The clinical value of whole brain radiotherapy (WBRT) for brain metastases (BM) is a matter of debate due to the significant side effects involved. Stereotactic radiosurgery (SRS) is an attractive alternative treatment option that may avoid these side effects and improve local tumor control. We initiated a randomized trial (NCT02353000) to investigate whether quality of life is better preserved after SRS compared with WBRT in patients with multiple brain metastases. Methods Patients with 4 to 10 BM were randomized between the standard arm WBRT (total dose 20 Gy in 5 fractions) or SRS (single fraction or 3 fractions). The primary endpoint was the difference in quality of life (QOL) at three months post-treatment. Results The study was prematurely closed due to poor accrual. A total of 29 patients (13%) were randomized, of which 15 patients have been treated with SRS and 14 patients with WBRT. The median number of lesions were 6 (range, 4-9) and the median total treatment volume was 13.0 cc 3 (range, 1.8-25.9 cc 3). QOL at three months decreased in the SRS group by 0.1 (SD=0.2), compared to 0.2 (SD=0.2) in the WBRT group (p=0.23). The actuarial one-year survival rates were 57% (SRS) and 31% (WBRT) (p=0.52). The actuarial one-year brain salvage-free survival rates were 50% (SRS) and 78% (WBRT) (p=0.22). Conclusion In patients with 4 to 10 BM, SRS alone resulted in one-year survival for 57% of patients while maintaining quality of life. Due to the premature closure of the trial, no statistically significant differences could be determined.

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