Leon Jekel

Background: Tumor Treating Fields improve survival when started after chemoradiotherapy in newly diagnosed glioblastoma, but the safety and feasibility of initiating treatment before and during radiotherapy remain uncertain. Methods: PriCoTTF is a prospective, open-label, nonrandomized, multicenter phase I/II trial. Arm A enrolled adults aged 18 to 70 years with newly diagnosed IDH-wildtype glioblastoma or gliosarcoma, Karnofsky Performance Status of at least 60, and planned focal radiotherapy to 60 Gy in 30 fractions. TTFields at 200 kHz were initiated 2 to 4 weeks after surgery and 1 to 2 weeks before radiotherapy. The primary endpoint was protocol-defined treatment-limiting toxicity from TTFields initiation through 4 weeks after radiotherapy. Results: Twenty evaluable patients comprised the Arm A feasibility cohort. No protocol-defined treatment-limiting toxicities occurred (0 of 20 patients; exact 95% CI, 0.0%-16.8%). Grade 3 or higher adverse events occurred in 12 patients (60%), predominantly hematologic toxicity attributable to chemoradiotherapy; lymphopenia occurred in 6 patients (30%). Median usage through visit 4 was 76.5%, and median time to first attainment of at least 75% daily use was 2 days. Median progression-free survival was 6.9 months (95% CI, 2.7–14.0), and median overall survival was 18.0 months (95% CI, 12.1–19.9). Conclusions: Initiation of TTFields before and during radiotherapy was feasible and was not associated with protocol-defined treatment-limiting toxicity in the Arm A cohort. Because the TLT definition was narrow and efficacy analyses were exploratory and exposure-conditioned, these findings should be interpreted as feasibility data rather than evidence of improved tumor control or survival. The results support randomized evaluation of earlier TTFields integration in newly diagnosed glioblastoma. Trial registration: German Clinical Trials Register DRKS00016667, registered 26 February 2019.

Background: Patients with primary brain tumors face profound disease- and treatment-related immunosuppression, placing them at high risk for severe infections. Their capacity to mount protective immune responses to vaccination, particularly to repeated antigen exposures such as COVID-19 boosters, remains critically under-defined, leading to uncertainty in clinical practice. Methods: In this prospective cohort study, we analyzed humoral responses to seasonal COVID-19 (mRNA-based) and influenza vaccination in 17 patients with primary brain tumors (recruited from an initial cohort of 37) who received a booster shot, and 19 healthy controls. Serum samples were collected before (T1) and 30 ± 2 days after (T2) vaccination to quantify SARS-CoV-2 anti-Spike (S) IgG and anti-Influenza IgG titers. Results: Despite ongoing chemotherapy in 47% of patients, baseline anti-S antibody titers were comparable between groups. Following the booster, median anti-S titers increased significantly and to a similar magnitude in both patients (from 5030 to 18,500 BAU/mL; IQR: 13,885–24,420) and controls (from 4429 to 20,200 BAU/mL; IQR: 11,075–26,680; p = 0.6137, Mann–Whitney U test). Only two heavily pre-treated patients showed no booster response. All participants showed sero-positivity to Anti-Influenza IgG at baseline. For the primary brain tumor cohort, a significant increase for anti-Influenza IgG at T2 was observed (p = 0.0002). Mean antibody titers did not differ between both cohorts. Conclusions: Our findings provide evidence that patients with primary brain tumors can mount robust recall immunity to mRNA vaccines, addressing clinical uncertainty about booster efficacy in this population. These data provide a strong rationale for prioritizing booster vaccinations in this vulnerable population and argue for the inclusion of these patients in future pivotal vaccine trials.