First multicentric real-life experience with the combination of CCNU and temozolomide in newly diagnosed MGMT promoter methylated IDH wildtype glioblastoma.

Background: The randomized phase 3 CeTeG/NOA-09 trial assessed whether CCNU plus temozolomide was superior to temozolomide alone in newly diagnosed MGMT promoter methylated glioblastoma patients. Survival was significantly improved from 31.4 months (temozolomide) to 48.1 months (CCNU plus temozolomide). In view of this encouraging data, we assessed safety and efficacy of this regimen under real-life conditions. Methods: We retrospectively collected clinical and radiographic data from adult newly diagnosed MGMT promoter methylated IDH wildtype glioblastoma patients from five neuro-oncology centers in Germany. For inclusion in our analysis, treatment with CCNU and temozolomide had to be performed for at least six weeks (one course). Results: Seventy patients were included. Median progression-free survival was 14.4 months and median overall survival 33.8 months. Patients with TTFields treatment for at least 8 weeks and CCNU plus temozolomide (n = 22, 31%) had a prolonged progression-free survival compared to those with TTFields treatment for less than eight weeks (n = 48, 69%) (21.5 versus 11.2 months; P = .0105). In a multivariable Cox regression analysis, TTFields treatment for eight weeks or longer together with CCNU plus temozolomide and a Karnofsky performance score ≥ 90% were independent prognostic factors for progression-free and overall survival. Pseudoprogression occurred in n = 16 (33%) of investigated n = 49 (70%) patients. In n = 31 (44%) patients high-grade hematotoxicity was observed. Conclusions: The results from this multicentric trial indicate that-under real-life conditions-toxicity and survival estimates are comparable to the CeTeG/NOA-09 trial. TTFields therapy for at least eight weeks in combination with this regimen was independently associated with prolonged survival.

Spinal meningiomas - Risks and potential of an increasing age at the time of surgery.

Although the majority of surgeries for spinal meningiomas are performed in geriatric patients, age-related analyzes of preoperative symptoms and functional outcome are sparse. Clinical, neuropathological and radiological data of 88 patients who underwent surgery for spinal meningiomas were reviewed. Correlations between the patients' age and preoperative symptoms as well as functional outcome were investigated. 14 males (16%) and 74 females (84%) with a median age of 67 years were included. Age at the time of surgery was independent of the tumor location and volume, intra-/extradural tumor location, spinal cord compression or signal change on T2-weighted MRI (p > 0.05, each). Preoperative McCormick score (p = 0.001), motor (p = 0.005) and sensory (p = 0.025) deficits and incontinence (p = 0.010) increased, while frequency of radicular pain decreased with increasing age (p = 0.020). Multivariate analyses confirmed an increasing risk of motor (OR: 1.05, p = 0.017) and, with borderline significance, of sensory deficits (OR: 1.04, 95%CI 1.00-1.10; p = 0.056) with rising age. Simpson grades I, II, III and IV were achieved in 12 (14%), 54 (64%), 14 (17%) and 4 (5%) individuals, respectively. Only 3 of 12 patients (25%) with perioperative complications were younger than 65 years. Rising age was associated with improvement of motor (p = 0.006) and sensory deficits (p = 0.045). In multivariate analyzes, probability of improvement of preoperative motor weakness (OR = 1.05, p = 0.031) and sensory deficits (OR = 1.07, p = 0.014) increased with rising age. Despite more frequent preoperative neurological deficits, older patients with spinal meningiomas recover most noticeably after surgery. However, stratification of the medical condition is urgent to reduce complications.