Abstract
Abstract Background: Preclinical studies with transplanted GL261 glioma in mouse brain treated with radiosurgery and checkpoint blockade showed dramatic improvement of tumor cure and prolonged survival, associated with activated macrophage infiltration in the tumor site. We perform phase I study in patients with glioblastoma to assess safety and local tumor response by combined radiosurgery and checkpoint inhibitor given during window-of-opportunity prior to surgical resection, and progression-free survival and overall survival. Method and Procedure: Biopsy-proven WHO grade 4 glioblastoma patients were enrolled to the study (NCT05423210). Patients were treated with two doses of intravenous Atezolizumab at the beginning and at the end of the two-week period, concomitantly with fractionated radiosurgery (8 Gy x 4 to the grossly enhancing tumor) over 4 days during the course of 2 weeks. Maximal safe surgical resection was subsequently performed within 2 weeks from completion of radiosurgery. Adjuvant radiation 50 Gy over 5 weeks and Temozolomide were given as per standard treatment of GBM along with continuation of Atezolizumab until unacceptable toxicity or tumor progression. The initial biopsy specimen and surgical specimen were collected for laboratory examination of immune profiles. Results: The study plans to enroll total 12 histologically confirmed CNS WHO Grade 4 GBM patients also planned for surgical resection. Six patients were enrolled after consenting so far. There was no grade 3 or 4 toxicity from the window-of-opportunity combination treatment, all 6 patients successfully completing the treatment. Three patients reported fatigue and two patients had skin rash. There was one patient experiencing metallic taste. At present, five patients survive progression-free at 25, 18, 16 and 6 months since the treatment. An unanticipated finding is that there was significantly less intraoperative bleeding in the surgical field than usual brain tumor surgery. Conclusion: Preoperative fractionated radiosurgery and Atezolizumab was well tolerated so far, and appear to improve tumor control. We continue enroll the patients. Lab study of immune cell profile is underway. Citation Format: Samuel Ryu, Alexander Stessin, Charles Mikell, Agnieszka Kowalska, Roberta Seidman, Steven West, Kartik Mani. Interim report of Phase I study of window-of-opportunity fractionated stereotactic radiotherapy combined with checkpoint blockade prior to surgical resection for newly diagnosed glioblastoma. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr B010.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call