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.

Radiotherapy in Medulloblastoma-Evolution of Treatment, Current Concepts and Future Perspectives.

Medulloblastoma is the most frequent malignant brain tumor in children. During the last decades, the therapeutic landscape has changed significantly with craniospinal irradiation as the backbone of treatment. Survival times have increased and treatments were stratified according to clinical and later molecular risk factors. In this review, current evidence regarding the efficacy and toxicity of radiotherapy in medulloblastoma is summarized and discussed mainly based on data of controlled trials. Current concepts and future perspectives based on current risk classification are outlined. With the introduction of CSI, medulloblastoma has become a curable disease. Due to combination with chemotherapy, survival rates have increased significantly, allowing for a reduction in radiation dose and a decrease of toxicity in low- and standard-risk patients. Furthermore, modern radiotherapy techniques are able to avoid side effects in a fragile patient population. However, high-risk patients remain with relevant mortality and many patients still suffer from treatment related toxicity. Treatment needs to be continually refined with regard to more efficacious combinatorial treatment in the future.

Enhancing the Outcome of Traumatic Sensory Nerve Lesions of the Hand by Additional Use of a Chitosan Nerve Tube in Primary Nerve Repair: A Randomized Controlled Bicentric Trial.

BACKGROUND: Peripheral sensory nerve injuries present a significant yet common challenge in acute hand trauma surgery. Standard treatment remains microsurgical end-to-end nerve repair where appropriate. Permanent loss of sensitivity and painful neuroma formation are typical sequelae of unsuccessful surgery. The objective of this study was to evaluate whether the additional use of a chitosan nerve tube in primary nerve repair positively influences sensory recovery. METHODS: A randomized, controlled, two-center trial with parallel group design and double-blind assessment was conducted to demonstrate the superiority of the additional use of a chitosan nerve tube compared with microsurgical nerve repair alone. Seventy-four participants were enrolled. The primary outcome parameter used was degree of static two-point discrimination at 6 months after surgery. Additional secondary outcome parameters included filament recognition testing (Semmes-Weinstein); pain; neuroma development; and the Disabilities of the Arm, Shoulder and Hand score. RESULTS: Nerve repair with additional use of chitosan nerve tubes (intervention group) significantly increased both tactile gnosis (expressed by two-point discrimination) and sensitivity (expressed by Semmes-Weinstein testing). The mean two-point discrimination at 6-month follow-up was 8 mm (range, 2 to 20 mm) in the control group and 6.3 mm (range, 1 to 15 mm) in the intervention group, respectively (p = 0.029). Two-point discrimination correlated with the Disabilities of the Arm, Shoulder and Hand score. In the control and intervention groups, respectively, three versus zero neuromas were found. CONCLUSIONS: Peripheral sensory nerve regeneration can be improved significantly by additional use of a chitosan nerve tube. An improved ability of static two-point discrimination is clinically relevant. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

Chitosan nerve tube for primary repair of traumatic sensory nerve lesions of the hand without a gap: study protocol for a randomized controlled trial.

BACKGROUND: Complex peripheral nerve injuries of the hand include at least 300,000 cases per year in Europe. The standard treatment involves a microsurgical end-to-end suture of traumatic sensory nerve lesions of the hand without a gap. The objective of this study protocol is to evaluate whether the additional use of a chitosan nerve tube in primary repair of traumatic sensory nerve lesions of the hand without a gap has an effect on the recovery of sensitivity. METHODS/DESIGN: We planned a randomized double-blind controlled multicenter trial with a parallel group design in order to show superiority for the additional use of a chitosan nerve tube. This study will enroll 100 participants with traumatic sensory nerve lesions of the hand without a gap from three Trauma Care Centers. Participants will be randomized in a 1:1 ratio to primary microsurgical repair of the injured nerve with the additional use of a chitosan nerve tube or direct tension free microsurgical repair of the injured nerve alone. The static two-point discrimination of the injured finger after 6 months will be the primary outcome parameter. DISCUSSION: In the proposed study, the additional use of a chitosan nerve tube for a primary microsurgical repair of traumatic sensory nerve lesions of the hand without a gap will be evaluated in a prospective randomized double-blind controlled multicenter trial for the first time to create the highest possible evidence for the procedure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02372669 . Protocol Registration Receipt on 27 February 2015.