Sonodynamic therapy with chemo-radiotherapy in high-grade brainstem gliomas: A prospective phase IIa clinical trial

The treatment of high-grade brainstem gliomas (HBSGs), which are a type of malignant neoplasm, is challenging. There is a need to develop novel and effective therapeutic approaches for HBSGs. This study analyzed the data between sonodynamic therapy (SDT) group and control groups. 24 patients with HBSGs who were treated with the combination of SDT and Stupp regimen served as SDT group. Admitted patients (n = 39) during the same period in our hospital,receiving only the Stupp regimen served as the control group. Most SDT-related adverse events (AEs) were classified as grade 1-2, indicating manageable safety risks. The incidence rates of severe AEs were not significantly different between the two groups. The median progression-free survival (PFS) and overall survival (OS) were not significantly different between the SDT and control groups. However, the 6-month PFS rate (P = 0.009), 1-year PFS rate (P = 0.021), objective response rate(ORR) (P = 0.044), median duration of disease control(DDC) (P = 0.002), median duration of response(DOR) (P = 0.010), and improvement in Karnofsky Performance Status(KPS) scores at month 1 post-treatment in the SDT group were significantly superior than those in the control group (P < 0.001). In the SDT group, the median OS of patients undergoing < 2 and ≥ 2 SDT cycles of treatment was 14.9 (95% CI: 6.9-22.9) and 20.9 months (95% CI: 16.5-25.3), respectively (P = 0.003). SDT and chemoradiotherapy combination was associated with favorable safety and dose-dependent survival benefit in patients with HBSGs, indicating its therapeutic potential.