Dataset Information

Stereotactic radiosurgery optimization with hippocampal-sparing in patients treated for brain metastases.

ABSTRACT:

Background and purpose

Cranial irradiation is associated with significant neurocognitive sequelae, secondary to radiation-induced damage to hippocampal cells. It has been shown that hippocampal-sparing (HS) leads to modest benefit in neurocognitive function in patients with brain metastases, but further improvement is possible. We hypothesized that improved benefits could be seen using HS in patients treated with stereotactic radiation (HS-SRS). Our study evaluated whether the hippocampal dose could be significantly reduced in the treatment of brain metastases using SRS, while maintaining target coverage.

Materials and methods

Sixty SRS plans were re-planned to minimize dose to the hippocampus while maintaining target coverage. Patients with metastases within 5 mm of the hippocampus were excluded. Minimum, mean, maximum and dose to 40% (mean equivalent dose in 2 Gy per fraction, EQD₂ to the hippocampus) were compared between SRS and HS-SRS plans. Median number of brain metastases was two.

Results

Compared to baseline SRS plans, hippocampal-sparing plans demonstrated D_min was reduced by 35%, from 0.4 Gy to 0.3 Gy (p-value 0.02). Similarly, D_max was reduced by 55%, from 8.2 Gy to 3.6 Gy, D_mean by 52%, from 1.6 Gy to 0.5 Gy, and D₄₀ by 50%, from 1.8 Gy to 0.9 Gy (p-values <0.001).

Conclusions

Our study demonstrated that further reduction of hippocampal doses of more than 50% is possible in the treatment of brain metastases with SRS using dose optimization. This could result in significantly improved neurocognitive outcomes for patients treated for brain metastases.

SUBMITTER: Burgess L

PROVIDER: S-EPMC8058021 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Introduction:Due to the neurocognitive side effects of whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS) is being used with increasing frequency. The use of SRS is expanding for patients with multiple (>4) brain metastases (BM). This study summarizes our institutional experience with single-fraction, linear-accelerator-based SRS for multiple BM. Methods and materials:All patients who were treated between January 1, 2013, and September 30, 2015, with single-fraction SRS for ?4 BM were included in this institutional review board-approved, retrospective, single-institution study. Patients were treated with linear accelerator-based image guided SRS. Results:A total of 59 patients with ?4 BM were treated with single-fraction SRS. The median follow-up was 15.2 months, and the median overall survival for the entire cohort was 5.8 months. The median number of treated lesions per patient was 5 (range, 4-23). Per patient, the median planning target volume (PTV) was 4.8?cc (range, 0.7-28.8?cc). The prescribed dose across all 380 BM for the 59 patients ranged from 7 to 20?Gy. The median of the mean dose to the total PTV was 19.5?Gy. Although the number of treated lesions (4-5 vs ?6) did not influence survival, better survival was noted for a total PTV <10?cc versus ?10?cc (7.1 vs 4.2 months, respectively; P?=?.0001). A mean dose of ?19?Gy to the entire PTV was also associated with increased survival (6.6 vs 5.0 months, respectively; P?=?.0172). Patients receiving a dose of >12?Gy to ?10?cc of normal brain had worse survival (5.1 vs 8.6 months, respectively; P?=?.0028). Conclusion:In single-fraction SRS for patients with multiple BM, smaller total tumor volume, higher total dose, and lower volume of normal brain receiving >12?Gy were associated with increased survival. These data suggest that using SRS for the treatment of multiple BM is efficacious and that outcomes may be affected more by total tumor volume than by the number of lesions.

Project description:BackgroundStereotactic radiosurgery (SRS) is a frequently chosen treatment for patients with brain metastases and the number of long-term survivors is increasing. Brain necrosis (e.g. radionecrosis) is the most important long-term side effect of the treatment. Retrospective studies show a lower risk of radionecrosis and local tumor recurrence after fractionated stereotactic radiosurgery (fSRS, e.g. five fractions) compared with stereotactic radiosurgery in one or three fractions. This is especially true for patients with large brain metastases. As such, the 2022 ASTRO guideline of radiotherapy for brain metastases recommends more research to fSRS to reduce the risk of radionecrosis. This multicenter prospective randomized study aims to determine whether the incidence of adverse local events (either local failure or radionecrosis) can be reduced using fSRS versus SRS in one or three fractions in patients with brain metastases.MethodsPatients are eligible with one or more brain metastases from a solid primary tumor, age of 18 years or older, and a Karnofsky Performance Status ≥ 70. Exclusion criteria include patients with small cell lung cancer, germinoma or lymphoma, leptomeningeal metastases, a contraindication for MRI, prior inclusion in this study, prior surgery for brain metastases, prior radiotherapy for the same brain metastases (in-field re-irradiation). Participants will be randomized between SRS with a dose of 15-24 Gy in 1 or 3 fractions (standard arm) or fSRS 35 Gy in five fractions (experimental arm). The primary endpoint is the incidence of a local adverse event (local tumor failure or radionecrosis identified on MRI scans) at two years after treatment. Secondary endpoints are salvage treatment and the use of corticosteroids, bevacizumab, or antiepileptic drugs, survival, distant brain recurrences, toxicity, and quality of life.DiscussionCurrently, limiting the risk of adverse events such as radionecrosis is a major challenge in the treatment of brain metastases. fSRS potentially reduces this risk of radionecrosis and local tumor failure.Trial registrationClincalTrials.gov, trial registration number: NCT05346367 , trial registration date: 26 April 2022.

Project description:Abstract Background Brain metastases (BM) are the most frequent neoplasm in the central nervous system (CNS) and primary tumors frequently involved are melanoma, lung cancer and breast cancer. CNS localisation is associated with poor prognosis, and stereotactic radiosurgery (SRS) represents a treatment option for patients with a good performance status. Glutamate (Glu) is a neurotransmitter which plays a facilitating role in carcinogenesis and progression of malignant tumors, as well as in excitotoxicity. Glu efflux from the brain is regulated by scavengers glutamic oxaloacetic transaminase (GOT), glutamate-pyruvate transaminase (GPT) and lactate dehydrogenase (LDH), with aspartate and lactate as catabolites. Glu efflux from the brain seems to be impaired in advanced-stage cancers, resulting in increased blood Glu levels where scavengers exert a protective role. Our hypothesis is that serum Glu and scavengers’ levels are related to neuroinvasion and treatment response in patients with BM and may represent potential biomarkers for BM course and prognosis. Material and Methods Serum Glu scavengers (GOT1, GPT and LDH), serum Glu, aspartate and lactate levels are collected in included patients treated and grouped in A) BM group of patients affected by BM from lung or breast cancer or melanoma, treated with SRS; B) Control-1 group of patients affected by lung cancer, breast cancer or melanoma but without BM and C) Control-2 group of patients with benign intracranial lesions (meningiomas, acoustic schwannomas) treated with SRS.In A) and C) serum metabolites and scavengers will be analyzed before and after SRS treatment (at 3, 6, 9 months) while in B) analyzed once. Blood levels in A) and C) help in identifying differences related to malignancy, the role of SRS and the association with disease control, while blood levels in A) and B) help in detecting differences related to BMs. Exclusion criteria are surgical or previous radiosurgical treatment for BM. This study has received Institutional Ethical Committee approval on 3rd August 2020 (Project NCH04-2020, Clinicaltrials.gov identifier: NCT04785521). Preliminary results Comparison between BM group (n = 32) and Control-1 (n=18) revealed a significant difference in LDH (271.93 vs 217.56 U/L; p 0.041) and lactate (1.86 vs 1.34 mmol/L, p = 0.022) and a trend towards significance in glutamate (103.43 vs 73.74 µmol/L, p = 0.07). Comparison between BM group (n=32) and Control-2 (n = 37) revealed a difference in LDH (271.93 vs 210.89 U/L; p < 0.001), lactate (1.86 vs 1.24 mmol/L; p < 0.001), aspartate (16.36 vs 10.22 µmol/L, p 0.006) and glutamate levels (123 vs 103 µmol/L, p = 0.052). Conclusion The present study is the first one addressing serum glutamate and scavenger levels in patients with BM. If the hypothesis will be confirmed, new targets in glutamate signalling pathway could be identified to define new therapeutic strategies in this challenging disease.