Dataset Information

Neuroinflammation After Stereotactic Radiosurgery-Induced Brain Tumor Disintegration Is Linked to Persistent Cognitive Decline in a Mouse Model of Metastatic Disease.

ABSTRACT:

Purpose

Improved efficacy of anticancer therapy and a growing pool of survivors give rise to a question about their quality of life and return to premorbid status. Radiation is effective in brain metastasis eradication, although the optimal approach and long-term effects on brain function are largely unknown. We studied the effects of radiosurgery on brain function.

Methods and materials

Adult C57BL/6J mice with or without brain metastases (rat 9L gliosarcoma) were treated with cone beam single-arc stereotactic radiosurgery (SRS; 40 Gy). Tumor growth was monitored using bioluminescence, whereas longitudinal magnetic resonance imaging, behavioral studies, and histologic analysis were performed to evaluate brain response to the treatment for up to 18 months.

Results

Stereotactic radiosurgery (SRS) resulted in 9L metastases eradication within 4 weeks with subsequent long-term survival of all treated animals, whereas all nontreated animals succumbed to the brain tumor. Behavioral impairment, as measured with a recognition memory test, was observed earlier in mice subjected to radiosurgery of tumors (6 weeks) in comparison to SRS of healthy brain tissue (10 weeks). Notably, the deficit resolved by 18 weeks only in mice not bearing a tumor, whereas tumor eradication was complicated by the persistent cognitive deficits. In addition, the results of magnetic resonance imaging were unremarkable in both groups, and histopathology revealed changes. SRS-induced tumor eradication triggered long-lasting and exacerbated neuroinflammatory response. No demyelination, neuronal loss, or hemorrhage was detected in any of the groups.

Conclusions

Tumor disintegration by SRS leads to exacerbated neuroinflammation and persistent cognitive deficits; therefore, methods aiming at reducing inflammation after tumor eradication or other therapeutic methods should be sought.

SUBMITTER: Chu C

PROVIDER: S-EPMC8758056 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionNeoadjuvant stereotactic radiosurgery (NaSRS) of brain metastases has gained importance, but it is not routinely performed. While awaiting the results of prospective studies, we aimed to analyze the changes in the volume of brain metastases irradiated pre- and postoperatively and the resulting dosimetric effects on normal brain tissue (NBT).MethodsWe identified patients treated with SRS at our institution to compare hypothetical preoperative gross tumor and planning target volumes (pre-GTV and pre-PTV) with original postoperative resection cavity volumes (post-GTV and post-PTV) as well as with a standardized-hypothetical PTV with 2.0 mm margin. We used Pearson correlation to assess the association between the GTV and PTV changes with the pre-GTV. A multiple linear regression analysis was established to predict the GTV change. Hypothetical planning for the selected cases was created to assess the volume effect on the NBT exposure. We performed a literature review on NaSRS and searched for ongoing prospective trials.ResultsWe included 30 patients in the analysis. The pre-/post-GTV and pre-/post-PTV did not differ significantly. We observed a negative correlation between pre-GTV and GTV-change, which was also a predictor of volume change in the regression analysis, in terms of a larger volume change for a smaller pre-GTV. In total, 62.5% of cases with an enlargement greater than 5.0 cm3 were smaller tumors (pre-GTV < 15.0 cm3), whereas larger tumors greater than 25.0 cm3 showed only a decrease in post-GTV. Hypothetical planning for the selected cases to evaluate the volume effect resulted in a median NBT exposure of only 67.6% (range: 33.2-84.5%) relative to the dose received by the NBT in the postoperative SRS setting. Nine published studies and twenty ongoing studies are listed as an overview.ConclusionPatients with smaller brain metastases may have a higher risk of volume increase when irradiated postoperatively. Target volume delineation is of great importance because the PTV directly affects the exposure of NBT, but it is a challenge when contouring resection cavities. Further studies should identify patients at risk of relevant volume increase to be preferably treated with NaSRS in routine practice. Ongoing clinical trials will evaluate additional benefits of NaSRS.

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