A state-of-the-art review and guidelines for tumor treating fields treatment planning and patient follow-up in glioblastoma.
Ontology highlight
ABSTRACT:
SUBMITTER: Trusheim J
PROVIDER: S-EPMC6027938 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Tumor treating fields (TTFields) is an anti-cancer technology increasingly used for the treatment of glioblastoma. Recently, cranial burr holes have been used experimentally to enhance the intensity (dose) of TTFields in the underlying tumor region. In the present study, we used computational finite element methods to systematically characterize the impact of the burr hole position and the TTFields transducer array layout on the TTFields distribution calculated in a realistic human head model. We investigated a multitude of burr hole positions and layouts to illustrate the basic principles of optimal treatment planning. The goal of the paper was to provide simple rules of thumb for physicians to use when planning the TTFields in combination with skull remodeling surgery. Our study suggests a number of key findings, namely that (1) burr holes should be placed directly above the region of interest, (2) field enhancement occurs mainly underneath the holes, (3) the ipsilateral array should directly overlap the holes and the contralateral array should be placed directly opposite, (4) arrays in a pair should be placed at far distance and not close to each other to avoid current shunting, and finally (5) rotation arrays around their central normal axis can be done without diminishing the enhancing effect of the burr holes. Minor deviations and adjustments (<3 cm) of arrays reduces the enhancement to some extent although the procedure is still effective in these settings. In conclusion, our study provides simple guiding principles for implementation of dose-enhanced TTFields in combination with burr-holes. Future studies are required to validate our findings in additional models at the patient specific level.
| S-EPMC9245346 | biostudies-literature
Project description:Glioblastoma (GBM) is one of the most common tumors of the central nervous system, which is the most lethal brain cancer. GBM treatment is based primarily on surgical resection, combined with radiotherapy and chemotherapy. Despite the positive treatment, progression free survival and overall survival were not significantly prolonged because GBM almost always recurs. We are always looking forward to some new and effective treatments. In recent years, a novel treatment method called tumor treating fields (TTFields) for cancer treatment has been proposed. TTFields devices were approved by the Food and Drug Administration (FDA) for adjuvant treatment of recurrent and newly diagnosed GBMs in 2011 and 2015, respectively. This became the first breakthrough treatment for GBM in the past 10 years after the FDA approved bevacizumab for patients with relapsed GBM in 2009. This paper summarized the research results of TTFields in recent years and elaborated the mechanism of action of TTFields on GBM, including cell and animal experimental research, clinical application and social benefits.
| S-EPMC7671789 | biostudies-literature
Project description:Background:Tumor Treating Fields (TTF) have entered clinical practice for newly diagnosed and recurrent glioblastoma (GGM). However, controversies remain unresolved with regard to appropriate usage. We sought to determine TTF usage in major academic neuro-oncology programs in New York City, USA and Heidelberg, Germany and understand current attitudes toward TTF usage among providers. Methods:We retrospectively determined TTF usage among patients with GGM, before and since the publication of key clinical trial results and regulatory approvals. We also surveyed attendees of an educational session related to TTF during the 2019 American Society of Clinical Oncology annual meeting. Results:TTF usage remains infrequent (3-12% of patients with newly diagnosed GBM, and 0-16% of patients with recurrent disease) in our practices, although it has increased over time. Among 30 survey respondents (77% of whom self-identified as neuro- or medical oncologists), 60% were convinced that TTF prolongs survival for newly diagnosed GGM despite published phase III data and regulatory approval, and only 30% viewed TTF as definitively part of the standard of care treatment. A majority (87%) opposed mandating TTF incorporation into the design of clinical trials. Conclusions:Providers continue to view TTF with some level of skepticism, with a lack of additional supportive data and logistical concerns representing continued barriers to uptake.
| S-EPMC7345837 | biostudies-literature
Project description:Glioblastoma is the most common yet most lethal of primary brain cancers with a one-year post-diagnosis survival rate of 65% and a five-year survival rate of barely 5%. Recently the U.S. Food and Drug Administration approved a novel fourth approach (in addition to surgery, radiation therapy, and chemotherapy) to treating glioblastoma; namely, tumor treating fields (TTFields). TTFields involves the delivery of alternating electric fields to the tumor but its mechanisms of action are not fully understood. Current theories involve TTFields disrupting mitosis due to interference with proper mitotic spindle assembly. We show that TTFields also alters cellular membrane structure thus rendering it more permeant to chemotherapeutics. Increased membrane permeability through the imposition of TTFields was shown by several approaches. For example, increased permeability was indicated through increased bioluminescence with TTFields exposure or with the increased binding and ingress of membrane-associating reagents such as Dextran-FITC or ethidium D or with the demonstration by scanning electron microscopy of augmented number and sizes of holes on the cellular membrane. Further investigations showed that increases in bioluminescence and membrane hole production with TTFields exposure disappeared by 24?h after cessation of alternating electric fields thus demonstrating that this phenomenom is reversible. Preliminary investigations showed that TTFields did not induce membrane holes in normal human fibroblasts thus suggesting that the phenomenom was specific to cancer cells. With TTFields, we present evidence showing augmented membrane accessibility by compounds such as 5-aminolevulinic acid, a reagent used intraoperatively to delineate tumor from normal tissue in glioblastoma patients. In addition, this mechanism helps to explain previous reports of additive and synergistic effects between TTFields and other chemotherapies. These findings have implications for the design of combination therapies in glioblastoma and other cancers and may significantly alter standard of care strategies for these diseases.
| S-EPMC6281619 | biostudies-literature
Project description:Sarcoidosis + Follow-up 6 month after Keywords = sarcoidosis Keywords = follow-up Keywords: other
2005-01-18 | GSE1907 | GEO
Project description:Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults and continues to portend poor survival, despite multimodal treatment using surgery and chemoradiotherapy. The addition of tumour-treating fields (TTFields)-an approach in which alternating electrical fields exert biophysical force on charged and polarisable molecules known as dipoles-to standard therapy, has been shown to extend survival for patients with newly diagnosed GBM, recurrent GBM and mesothelioma, leading to the clinical approval of this approach by the FDA. TTFields represent a non-invasive anticancer modality consisting of low-intensity (1-3 V/cm), intermediate-frequency (100-300 kHz), alternating electric fields delivered via cutaneous transducer arrays configured to provide optimal tumour-site coverage. Although TTFields were initially demonstrated to inhibit cancer cell proliferation by interfering with mitotic apparatus, it is becoming increasingly clear that TTFields show a broad mechanism of action by disrupting a multitude of biological processes, including DNA repair, cell permeability and immunological responses, to elicit therapeutic effects. This review describes advances in our current understanding of the mechanisms by which TTFields mediate anticancer effects. Additionally, we summarise the landscape of TTFields clinical trials across various cancers and consider how emerging preclinical data might inform future clinical applications for TTFields.
| S-EPMC7884384 | biostudies-literature
Project description:BackgroundTumor 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.MethodsTen 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.ResultsAfter 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.ConclusionsThis 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.
| S-EPMC6351720 | biostudies-literature
Project description:The advent of antiretroviral therapy (ART) in 1996 brought with it an urgent need to develop models of health care delivery that could enable its effective and equitable delivery, especially to patients living in poverty. Community-based care, which stretches from patient homes and communities-where chronic infectious diseases are often best managed-to modern health centers and hospitals, offers such a model, providing access to proximate HIV care and minimizing structural barriers to retention. We first review the recent literature on community-based ART programs in low- and low-to-middle-income country settings and document two key principles that guide effective programs: decentralization of ART services and long-term retention of patients in care. We then discuss the evolution of the community-based programs of Partners In Health (PIH), a nongovernmental organization committed to providing a preferential option for the poor in health care, in Haiti and several countries in sub-Saharan Africa, Latin America, Russia and Kazakhstan. As one of the first organizations to treat patients with HIV in low-income settings and a pioneer of the community-based approach to ART delivery, PIH has achieved both decentralization and excellent retention through the application of an accompaniment model that engages community health workers in the delivery of medicines, the provision of social support and education, and the linkage between communities and clinics. We conclude by showing how PIH has leveraged its HIV care delivery platforms to simultaneously strengthen health systems and address the broader burden of disease in the places in which it works.
| S-EPMC5106499 | biostudies-literature
Project description:Alternating electric fields have been successfully applied to cancer cells in-vitro to disrupt malignant progression and this antimitotic therapy has now been proven to be efficacious in Phase II and Phase III randomized clinical trials of patients with glioblastoma. With additional clinical trials ongoing in a number of other malignancies, there is a crucial need for a better understanding of the radiographic predictors of response and standardization of surveillance imaging interpretation. However, many radiologists have yet to become familiarized with this emerging cancer therapy and there is little active investigation to develop prognostic or predictive imaging biomarkers. This article provides an overview of the pre-clinical data that elucidate the biologic mechanisms of alternating electric fields as a cancer therapy. Results from clinical trials in patients with glioblastoma are then reviewed while elaborating on the several limitations to adoption of this promising line of treatment. Finally, a proposal for the development of imaging markers as a means of overcoming some of these limitations is made, which may improve treatment utilization by augmenting patient selection not only in glioblastoma, but also other malignant conditions for which this therapy is currently being evaluated.
| S-EPMC6884888 | biostudies-literature