Speakers

Sulfasalazine as Radiosensitizer in combination with Stereotactic Radiosurgery for recurrent Glioblastoma – A phase 1 dose-escalation trial – NCT04205357
1108 14:20-14:30
Neuro-oncology/305
Title: Phase 1 Dose-Escalation Trial: Sulfasalazine as Radiosensitizer with Stereotactic Radiosurgery for Recurrent Glioblastoma Multiforme - NCT04205357 Background. Glioblastoma (GBM) is a highly aggressive and radioresistant cancer type with a poor prognosis. Sulfasalazine (SAS) inhibits the production of glutathione (GSH), a compound that shields tumors from radiation-induced oxidative stress. We aimed to assess safety and therapeutic potential of SAS when combined with Gamma Knife Radiosurgery (GKRS) for recurrent GBM. Methods: The trial used a 3+3 dose escalation design across four dose cohorts (1.5, 3.0, 4.5, or 6.0 g SAS). Patients received SAS once daily for 3 days before GKRS to deplete tumor GSH levels. Primary endpoint was safety. Secondary endpoints included quality of life (QOL), changes in tumor GSH levels and volumes measured by GSH-magnetic resonance spectroscopy and contrast-enhanced T1-weighted magnetic resonance imaging (RANO criteria). Patients who received GKRS outside the trial due to pandemic/vacations served as contemporary controls for radiological response, freedom from local tumor progression (FFTP), progression-free survival (PFS), and overall survival (OS). Findings: From May 2020 to September 2022, 12 patients were enrolled. No dose-limiting toxicity was observed. Two patients experienced asymptomatic grade 3 lymphocytopenia of less than 24 hours duration without need for intervention. All other adverse events were mild or moderate. QOL remained stable up to 6 months post GKRS. SAS resulted in a significant reduction in intratumoral GSH levels compared to the opposite healthy side of the brain. Best radiological response was progression in 9.1% compared to 81.8 % in the control cohort (p < 0.001). For trial patients median FFTP was 6.8 vs. 1.6 months (p < 0.001, ratio 4.3; 95% confidence interval (CI): 1.6 to -11.0, PFS 3.2 vs. 1.6 months (p = 0.009, ratio 2.0; 95% CI: 0.9 to 4.6) and OS 11.2 vs. 11.5 months (ratio: 0.97; 95% CI:0.4 to 2.2, p = 0.931) for controls. Interpretation: The combination of SAS and GKRS was safe and well-tolerated, with preliminary evidence of anti-tumor response that compares favorably to controls. These findings warrant further investigation in higher phase multicenter trials.

Long-term results of Gamma Knife Radiosurgery and Resection for growing Incidental Meningiomas or Continued Active Surveillance, a Prospective Cohort Study
1108 14:00-14:10
Neuro-oncology/305
Objective: Incidental meningiomas are increasingly common. There is no consensus on their management. The risk of tumor progression requiring intervention must be considered. Long-term prospective data on incidental meningiomas are sparse. We aim to evaluate the long-term outcomes of active surveillance and intervention for growing incidentally discovered meningiomas. Methods: A prospective database of 62 patients (70 tumors) was established in 2009. Due to growth, 41 (58.6 %) tumors were treated. Radiological and clinical data was obtained until September 2023. The results of long-term active surveillance (Group 1) and intervention with GKRS (Group 2) or surgery (Group 3) were analyzed. Results: The mean growth rate was higher prior to GKRS (2.1 cm3/year) and surgery (0.4 cm3/year) than during long-term active surveillance (0.009 cm3/year; p < 0.001). The meningiomas became in mean 31.3 % and 99.1 % smaller after GKRS and resection, respectively. In comparison, tumors in the long-term surveillance arm increased in mean 27.2 % (p < 0.001). According to the RANO response criteria, the complete, partial and minimal response versus stable disease rates were higher following intervention, the overall progressive disease rates were similar (Group 1; 20.7 %, group 2: 11.4 % and group 3: 16.7 %), p = 0.232. Treatment versus no-treatment did not affect overall survival (Group 1; 10.3 years, group 2: 11.8 years and group 3: 13.5 years p = 0.264), which was comparable to the general population. While no symptoms were registered in group 1, 2.9 % in group 2 experienced transient grade 2 and half of the patients suffered permanent grade 4 adverse events in group 3. Conclusion: Intervention effectively reduces tumor volume; however, the clinical significance remains uncertain and side effects are not negligible. Active surveillance is safe, saves >40 % of patients from unnecessary interventions and does not seem to compromise future treatments. The optimal timing and risk of intervention should be further explored in prospective randomized trials.