Background:
Tumor treating fields (TTFields) are a non-invasive antimitotic therapy that delivers alternating electric fields via the Optune® system. The Phase III EF-14 trial in newly diagnosed ...glioblastoma multiforme (GBM) showed significantly improved progression-free, overall and long-term survival when Optune was used together with maintenance temozolomide (TMZ) compared with TMZ alone. Compliance (average monthly use) was associated with better clinical outcome. The first-generation Optune system weighed approximately 6 pounds (~2.7 kg). The second-generation redesigned Optune system weighs 2.7 pounds (~1.2 kg). We tested and compared GBM patient experience with the second-generation system versus the first-generation system.
Methods:
Ten newly diagnosed and recurrent GBM patients in Germany (median age: 52.9 years 31-79) were prospectively monitored over the first month of transitioning from the first-generation to the second-generation Optune system. Questionnaires using a numerical analog scale assessed feedback at baseline (first generation) and after 1 month of second-generation use.
Results:
After transitioning to the second-generation system, compliance improved by more than 10% in four patients, was maintained in five patients and decreased by more than 10% in one patient. Following transition, eight out of nine patients reported a reduction in the triggering of malfunction alarms. Self-reported patient feedback showed improved handling and portability (weight, mobility) of the second- versus the first-generation Optune system.
Conclusions:
This patient user survey suggests that patient satisfaction with the second-generation Optune system is improved versus the first-generation system. Improved features of the new system help patients achieve and maintain a higher rate of treatment compliance.
Hepatocellular carcinoma (HCC), a highly aggressive liver cancer, is a leading cause of cancer-related death. Tumor Treating Fields (TTFields) are electric fields that exert antimitotic effects on ...cancerous cells. The aims of the current research were to test the efficacy of TTFields in HCC, explore the underlying mechanisms, and investigate the possible combination of TTFields with sorafenib, one of the few front-line treatments for patients with advanced HCC. HepG2 and Huh-7D12 human HCC cell lines were treated with TTFields at various frequencies to determine the optimal frequency eliciting maximal cell count reduction. Clonogenic, apoptotic effects, and autophagy induction were measured. The efficacy of TTFields alone and with concomitant sorafenib was tested in cell cultures and in an orthotopic N1S1 rat model. Tumor volume was examined at the beginning and following 5 days of treatment. At study cessation, tumors were weighed and examined by immunohistochemistry to assess autophagy and apoptosis. TTFields were found
to exert maximal effect at 150 kHz, reducing cell count and colony formation, increasing apoptosis and autophagy, and augmenting the effects of sorafenib. In animals, TTFields concomitant with sorafenib reduced tumor weight and volume fold change, and increased cases of stable disease following treatment versus TTFields or sorafenib alone. While each treatment alone elevated levels of autophagy relative to control, TTFields concomitant with sorafenib induced a significant increase versus control in tumor ER stress and apoptosis levels, demonstrating increased stress under the multimodal treatment. Overall, TTFields treatment demonstrated efficacy and enhanced the effects of sorafenib for the treatment of HCC
and
, via a mechanism involving induction of autophagy.
Objectives
The anatomy of the cavernous sinus is described controversially in a number of publications. In the present cadaveric study, the architecture of the dorsolateral wall of the cavernous ...sinus is studied microsurgically and histologically.
Materials and methods
Twenty cadaveric skulls have been dissected through a classical surgical frontotemporal approach. The temporal skull base was flattened and anatomical landmarks like the meningo-orbital band, superior orbital fissure, foramina rotundum, ovale, and spinosum were identified. Lateral of the trigeminal foramina, the dura was cut and the periosteal dural layer was separated from the meningeal layer, identifying an interdural zone. The length and the extent of this zone were evaluated. The dural architecture of the interdural incision zone was examined histologically.
Results
In all specimens, two dural layers lateral of the trigeminal foramina could be separated. The identified interdural incision zone extended in a length of 3.8–6.4 cm in the antero-posterior direction. The zone could be followed medially to the superior orbital fissure for 5.3 mm and lateral of the foramen spinosum for 6.4 mm. The separation of the dural layers allowed the approach to the superior border of the cavernous sinus through this interdural incision zone. The histological analysis of the interdural incision zone showed clearly the existence of two dural layers.
Conclusions
The architecture of the temporal-fossa-dura allows the microsurgical separation of two meningeal dural layers through a length of 5–6 cm next to the trigeminal foramina. Opening this interdural incision zone allowed exploring the superior border of the cavernous sinus.
Atlantoaxial dislocation in children is a very rare condition. We present the case of a dislocation happened during a break-dance maneuver. The purpose of this report is describing dangers of ...break-dancing and discussing the treatment we chose. The patient was followed up until 12 months after surgery. Magnetic resonance imaging and computed tomography of the cervical spine were evaluated. Translaminar fixation of C1/C2 had been performed after manual reposition under X-ray illumination. After a 12-month follow-up, the patient shows a stable condition without neurological dysfunction. He is not allowed to perform any extreme sports.
Purpose
Tumor Treating Fields (TTFields) are electric fields that disrupt cellular processes critical for cancer cell viability and tumor progression, ultimately leading to cell death. TTFields ...therapy is approved for treatment of newly-diagnosed glioblastoma (GBM) concurrent with maintenance temozolomide (TMZ). Recently, the benefit of TMZ in combination with lomustine (CCNU) was demonstrated in patients with O
6
-methylguanine DNA methyltransferase (MGMT) promoter methylation. The addition of adjuvant TTFields to TMZ plus CCNU further improved patient outcomes, leading to a CE mark for this regimen. The current in vitro study aimed to elucidate the mechanism underlying the benefit of this treatment protocol.
Methods
Human GBM cell lines with different
MGMT
promoter methylation statuses were treated with TTFields, TMZ, and CCNU, and effectiveness was tested by cell count, apoptosis, colony formation, and DNA damage measurements. Expression levels of relevant DNA-repair proteins were examined by western blot analysis.
Results
TTFields concomitant with TMZ displayed an additive effect, irrespective of MGMT expression levels. TTFields concomitant with CCNU or with CCNU plus TMZ was additive in MGMT-expressing cells and synergistic in MGMT-non-expressing cells. TTFields downregulated the FA-BRCA pathway and increased DNA damage induced by the chemotherapy combination.
Conclusions
The results support the clinical benefit demonstrated for TTFields concomitant with TMZ plus CCNU. Since the FA-BRCA pathway is required for repair of DNA cross-links induced by CCNU in the absence of MGMT, the synergy demonstrated in
MGMT
promoter methylated cells when TTFields and CCNU were co-applied may be attributed to the BRCAness state induced by TTFields.
Abstract
INTRODUCTION: TTFields are low intensity, intermediate frequency, alternating electric fields. The significant overall and progression-free survival benefit, shown in the EF-14 phase 3 study ...was seen in all patient-subgroups, independent of e.g. MGMT-promotor methylation-status or age. TTFields were not associated with additional systemic toxicity. At recurrence, patients were allowed to continue TTFields with second-line therapies. Here, we analyzed the safety data of TTFields + lomustine (CCNU) to evaluate safety and feasibility of this combination.
METHODS
Patients in the EF-14 trial received TTFields until second progression, or for 24 months. Change in chemotherapy regimen was allowed after tumor progression. We compared the patients who received lomustine as second-line chemotherapy in combination with TTFields (n=134) to the patients who received lomustine as monotherapy after first progression (n=39). We compared baseline characteristics and the adverse event profile between the groups.
RESULTS
Baseline characteristics were well balanced except for less female patients in the lomustine only group (7.7% vs. 22.4%). Median age in the TTFields/lomustine group was 55.5 years (29–83) compared to 50.0 years (19–71) for lomustine alone. The addition of TTFields to lomustine therapy was not associated with any significant increase in systemic adverse events compared to lomustine therapy alone (number of patients with 1 SAE 30 % vs. 31 %) and the distribution, severity and overall incidence of adverse events were not statistically different in patients in the two treatment groups. CONCLUSION: The data show that the combination of TTFields and lomustine is safe and feasible. This analysis emphasizes again the strong safety profile of TTFields and the high potential of combining TTFields with other modalities. This data is especially important in light of the recently presented, promising data from a small randomized trial that tested the combination of lomustine + TMZ in newly diagnosed (MGMT promotor-methylated only) glioblastoma patients.
Abstract
INTRODUCTION: Tumor Treating Fields (TTFields) are low intensity (1-3V/cm), intermediate frequency (100–300 KHz) alternating electrical fields approved for glioblastoma (GBM). In the EF-14 ...phase 3 study, TTFields showed a significant overall and progression-free survival benefit for patients with newly diagnosed GBM in combination with Temozolomide (TMZ). TTFields were not associated with systemic toxicity. At recurrence, patients continued TTFields with second line therapies. We analyzed the safety and feasibility of TTFields + lomustine (CCNU) combination.
Methods
Patients in the EF-14 trial received TTFields until second progression, or for 24 months. Change in chemotherapy regimen was allowed in both groups after tumor progression. We compared patients who received lomustine as second-line chemotherapy in combination with TTFields (n=134) to patients who received lomustine as monotherapy after first progression (n=39). We compared baseline characteristics and the adverse event profile between the two groups.
RESULTS
Baseline characteristics were well balanced; there were less female patients in the lomustine only group (7.7% vs. 22.4%). Median age in the TTFields/lomustine group was 55.5 years (29–83) versus 50.0 years (19–71) for lomustine alone. The addition of TTFields to lomustine therapy was not associated with any significant increase in rates of systemic adverse events compared to lomustine therapy alone (number of patients with ≥ 1 SAE 30 % vs. 31 %) and the distribution, severity and overall incidence of adverse events were not statistically different in patients in the two treatment groups. CONCLUSION: The combination of TTFields and lomustine is safe and feasible. This analysis emphasizes again the strong safety profile of TTFields and the high potential of combining TTFields with other therapy modalities. This data is especially important in light of the recently presented promising data from a small randomized trial that tested the combination of lomustine plus TMZ in newly diagnosed (MGMT promotor-methylated only) GBM patients.
Abstract
AIMS
Tumour Treating Fields (TTFields) are electric fields that disrupt processes required for cancer cell viability and tumour progression. TTFields therapy gained FDA approval and CE ...accreditation for newly diagnosed glioblastoma (ndGBM) following the EF-14 study (NCT00916409). We aimed to determine the real-world survival benefit of TTFields therapy.
METHOD
Survival data from clinical studies in TTFields therapy-treated patients with ndGBM were identified using a literature search and analysed. The Cochran Q test and Higgins I2 statistic were used to assess and quantify inter-study heterogeneity. Survival curves were pooled using a distribution-free random-effects method.
RESULTS
Among studies evaluating the clinical effcacy of TTFields therapy in ndGBM, six studies were identified which compared the addition of TTFields therapy to standard of care (SOC) vs SOC alone. The meta-analysis showed a significant improvement in OS for TTFields therapy-treated patients vs SOC alone (P < 0.001). The pooled effect was robust and independent of any individual study. In post-approval studies, the pooled median OS was 22.2 months (95% CI, 17.3–42.6) and 17.3 months (95% CI, 13.6–22.0) for TTFields therapy-treated patients and SOC, respectively. Rates of gross total resection were generally higher in the real-world setting, irrespective of TTFields therapy use. Average device usage of ≥75% was associated with prolonged survival vs <75% usage (pooled HR: 0.63; 95% CI, 0.48–0.83; P = 0.001).
CONCLUSIONS
Data suggest a significant survival benefit when TTFields therapy is added to SOC for patients with ndGBM. Usage of ≥75% may be meaningful in the real-world setting.
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