Sonodynamic therapy for adult-type diffuse gliomas: past, present, and future.

BACKGROUND: Intra-axial brain tumors persist as significant clinical challenges. Aggressive surgical resection carries risk of morbidity, and the blood-brain barrier (BBB) prevents optimal pharmacological interventions. There is a clear clinical demand for innovative and less invasive therapeutic strategies for patients, especially those that can augment established treatment protocols. Focused ultrasound (FUS) has emerged as a promising approach to manage brain tumors. Sonodynamic therapy (SDT), a subset of FUS, utilizes sonosensitizers activated by ultrasound waves to generate reactive oxygen species (ROS) and induce tumor cell death. OBJECTIVE: This review explores the historical evolution and rationale behind SDT, focusing on its mechanisms of action and potential applications in brain tumor management. METHOD: A systematic review was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Preclinical studies have demonstrated the efficacy of various sonosensitizers, including 5-aminolevulinic acid (5-ALA), fluorescein, porphyrin derivatives, and nanoparticles, in conjunction with FUS for targeted tumor therapy and BBB disruption. Clinical trials have shown promising results in terms of safety and efficacy, although further research is needed to fully understand the potential adverse effects and optimize treatment protocols. Challenges such as skull thickness affecting FUS penetration, and the kinetics of BBB opening require careful consideration for the successful implementation of SDT in clinical practice. Future directions include comparative studies of different sonosensitizers, optimization of FUS parameters, and exploration of SDT's immunomodulatory effects. CONCLUSION: SDT represents a promising frontier in the treatment of aggressive brain tumors, offering hope for improved patient outcomes.

Gamma Knife radiosurgery for gynecologic metastases to the brain: Analysis of pathology, survival, and tumor control.

OBJECTIVE: This study aims to evaluate the efficacy of stereotactic radiosurgery (SRS) in improving health outcomes of patients with gynecologic brain metastases. METHODS: Patients with gynecologic metastases treated with SRS from 2008 to 2020 were retrospectively reviewed. The median age at SRS was 63 years old (cervical 45.5, endometrial 65.5, ovarian 61). The median number of tumors was 3 (range 1-27), and cumulative tumor volume was 2.33 cc (range 0.03-45.63). Median margin dose prescribed was 16 Gy (range 14 Gy - 20 Gy). The median 12 Gy volume was 7.30 cc (range 0.21-74.14 cc). Outcome variables included overall survival (OS) after SRS, local tumor control (LTC), distant tumor control, and adverse radiation effect (ARE). RESULTS: Fifty patients (4 cervical, 25 endometrial, and 21 ovarian cancer) were identified. The OS at 6 and 12 months after SRS was 48%, and 44%, respectively. Eight patients (16%) died from CNS disease progression. The number of brain metastases (p = 0.011) and the Karnofsky Performance Scale (KPS) ≥ 70 (p = 0.020) were significant predictors of OS. LTC rate at 6 and 12 months were 92%, and 87%, respectively. Margin dose ≥16Gy correlated with significantly better local tumor control (p = 0.0001) without increased risk of ARE (p = 0.055). The risk of developing new metastases at 6 and 12 months were 12% and 24% respectively. SRS-induced ARE events occurred in 7 patients. CONCLUSION: Intracranial metastases from gynecologic malignancy can be effectively treated using SRS with low risk of neurotoxicity. Margin dose ≥16Gy can provide significantly better tumor control. Repeat SRS can be utilized to treat new metastases while avoiding the potential cognitive symptoms associated with WBRT.