Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
October 27th, 2014
A novel methodology that is employed for the treatment of recurrent glioblastomas is described. This treatment approach employs the application of alternating electric tumor treating fields (TTFields), known as TTF Therapy in combination with bevacizumab, a targeted agent that is currently FDA approved as monotherapy.
The overall goal of this procedure is to develop a technique whereby tumor treating fields or TT fields are applied concurrently with bevacizumab for the treatment of recurrent glioblastoma. This is accomplished by first using MRI data to generate a treatment layout. Next TTF system components are assembled and transducer arrays are applied to the scalp.
Then the TT fields are applied according to the treatment layout. Finally, bevacizumab is administered in a standard fashion, ultimately a follow-up MRI of the brain with gadolinium. DTPA is obtained in order to assess tumor response to this novel therapy.
Though this method can provide insight into the treatment resistant gliomas, it can also be applied in theory to other tumors such as brain metastases. Although currently the only FDA approved indication for TT fields is for recurrent glioblastomas. Generally healthcare providers new to this method will struggle because of the lack of familiarity with the TTF system and its proper operation.
They will therefore need special mandated certification provided by the manufacturer. The TTF system is composed of the following instruments, a portable battery, a connection cable, and a box, an electric field generator, a plugin power supply, and a set of transducer arrays. To assemble the TTF system, charge the battery by placing it in the charger, plugging in the charger to a wall outlet and turning on the power button on the back of the charger.
Once the battery has been charged, plug the battery into the electric field generator, then through its connector to a socket labeled DC Inn on the front panel of the device, ensure that the arrows on the battery connector are facing up towards the DC in sign while plugging in the connector. Then using the black and white color coded plugs, connect each of the four transducer array connectors to the matching black and white color coded sockets. On the connection cable box, insert the cable from the connection box to the connection cable socket on the device to apply the transducer array.
Begin by using an electric shaver to shave the patient's entire scalp, ensuring that no stubble remains. Then use 70%medical grade alcohol to wipe the scalp. Next, remove the transducer arrays from the envelopes.
Then to the patient's clean scalp. Apply each of the arrays according to a predetermined specific array arrangement. Plug the array cables into the color matched connection cable and box.
After the arrays are in place and the system is fully connected, turn on the power switch on the device, then switch on the TTF field button. The system is now ready for electric field delivery. Once the patient is deemed an appropriate candidate, administer the bevacizumab infusion at a standard dose of 10 milligrams per kilogram of body weight over 30 minutes while simultaneously running the TTF system.
Watch for infusion reactions and or side effects and manage accordingly per the written protocol shown. Here are results from treating a 56-year-old female with the off-label combination treatment of bevacizumab with TTF for approximately one month for an average of 10 to 12 hours per day after discontinuing the treatment due to the patient becoming progressively agitated. Follow-up imaging revealed that both enhancing as represented by MR Post gadolinium and non enhancing disease or the MR Flare sequence exhibited radiographic regression.
The exact mechanism underlying this tumor response is unclear. However, it is postulated that bevacizumab through reducing blood vessel leakiness and permeability may result in a decrease in gadolinium extravasation without affecting the non enhancing disease. We also postulate that the reduction in the non enhancing disease seen here in our patient is due to the tumor treating fields or perhaps the combination approach rather than a bevacizumab effect.
This is because bevacizumab is known to result in an increase rather than a decrease in the non enhancing disease with reducing the enhancing component. While attempting this procedure, it's important to remember to follow manufacturer safety instructions, IFU, and troubleshooting Following this procedure. Other methods like combining TT fields with other chemotherapeutic agents can be performed in order to answer additional questions like whether other chemotherapeutic agents act in a synergistic fashion with TT fields for the treatment of recurrent glioblastomas.
Overview
This article describes a novel methodology for treating recurrent glioblastomas using alternating electric tumor treating fields (TTFields) in combination with bevacizumab. The treatment aims to improve patient outcomes by utilizing MRI data for precise application of TT fields alongside standard bevacizumab administration.
Key Study Components
Area of Science
- Neuroscience
- Oncology
- Therapeutic Techniques
Background
- Recurrent glioblastomas are challenging to treat and often resistant to conventional therapies.
- TTFields have shown promise in targeting tumor cells through electric fields.
- Bevacizumab is an FDA-approved agent that targets vascular endothelial growth factor (VEGF).
- The combination of these therapies may enhance treatment efficacy.
Purpose of Study
- To develop a technique for concurrent application of TTFields and bevacizumab.
- To assess the effectiveness of this combination in treating recurrent glioblastomas.
- To explore the potential for this method to be applied to other tumor types.
Methods Used
- Utilization of MRI data to create a treatment layout for TTFields.
- Assembly of the TTF system components and application of transducer arrays to the scalp.
- Simultaneous administration of bevacizumab during TTField application.
- Follow-up MRI imaging to evaluate tumor response.
Main Results
- A case study demonstrated radiographic regression in a patient treated with the combination therapy.
- Follow-up imaging indicated changes in both enhancing and non-enhancing tumor components.
- The mechanism of response is hypothesized to involve reduced blood vessel leakiness due to bevacizumab.
- Further research is needed to clarify the effects of TTFields and their potential synergy with other agents.
Conclusions
- The combination of TTFields and bevacizumab presents a novel approach for treating recurrent glioblastomas.
- Healthcare providers must be trained in the operation of the TTF system for effective implementation.
- Future studies should investigate the broader applicability of this method to other tumor types.
Frequently Asked Questions
Executive Industry Relevance
This methodology addresses the unmet need for improved therapeutic options in recurrent glioblastoma by combining two FDA-approved modalities—tumor treating fields and bevacizumab—to potentially enhance treatment efficacy and patient outcomes. The approach supports preclinical and clinical evaluation of combination therapies in oncology, offering a framework for assessing synergistic mechanisms and radiographic response in treatment-resistant tumors. It enables early-phase investigation of novel therapeutic combinations with direct relevance to glioblastoma drug development pipelines.
Strategic Applications in Biopharma R&D
Early Discovery & Target Validation
- Scientific Value: Enables interrogation of therapeutic hypotheses by assessing tumor response to combined modality treatment in a clinically relevant model.
- Operational Value: Provides a standardized protocol for concurrent delivery of device-based and biologic therapies, supporting reproducible experimental design.
- Predictive Value: Facilitates mechanistic de-risking by allowing observation of effects on both enhancing and non-enhancing tumor components via MRI.
Screening & Assay Development
- Scientific Value: Supports development of quantitative imaging endpoints (e.g., MRI-based tumor regression) for evaluating therapeutic response in preclinical models.
- Operational Value: Establishes a workflow for integrating device-based field delivery with systemic agent administration, enabling assay standardization.
- Translational Value: Generates pharmacodynamic data on vascular normalization and tumor field effects, informing biomarker strategy.
Translational & Preclinical Research
- Scientific Value: Offers a disease-relevant system to study combination therapy effects in recurrent glioblastoma, a therapeutically challenging indication.
- Operational Value: Enables continuity from discovery through preclinical validation by using MRI as a translational readout across study phases.
- Risk Mitigation: Supports go/no-go decisions by providing early evidence of radiographic response and tolerability in a clinically translatable model.
Pipeline & Workflow Integration
The method fits within the oncology discovery continuum, supporting early evaluation of combination strategies from target validation through preclinical efficacy assessment before advancing to clinical investigation.
- Discovery Biology: Supports hypothesis testing regarding synergistic mechanisms between tumor treating fields and VEGF inhibition in glioblastoma.
- Screening: Describes assay readiness through standardized transducer array application and concurrent bevacizumab dosing, enabling reliable compound or modality evaluation.
- Analytics: Highlights MRI-based quantitative measurements (enhancing and non-enhancing disease) as key readouts for assessing tumor response and guiding go/no-go decisions.
- Translational Research: Connects discovery to preclinical continuity via imaging biomarkers that reflect vascular and tumor cellular responses.
- Enterprise Reuse: Presents a reusable platform for evaluating other device-drug combinations in oncology, particularly in CNS malignancies.
Operational & Enterprise Impact
- Scientific Value: Enhances predictive confidence by enabling dual-modality assessment of tumor response, reducing ambiguity in mechanistic interpretation.
- Operational Value: Promotes standardization through manufacturer-mandated training and standardized device setup, improving reproducibility across sites.
- Strategic Value: Supports better go/no-go decisions by providing early radiographic and clinical data on combination therapy effects, reducing late-stage failure risk.
- Portfolio Impact: Enables risk-adjusted prioritization of combination therapies in glioblastoma development portfolios based on mechanistic and response data.
Implementation Considerations
- Requires expertise in neuro-oncology, medical device operation, and infusion therapy administration.
- Depends on access to TTF system components, MRI infrastructure, and intravenous infusion capabilities.
- Necessitates cross-functional standardization between neurology, oncology, radiology, and biomedical engineering teams.
- Involves adaptation considerations for different patient anatomies and tumor locations when applying transducer arrays.
- Limited by the need for specialized training and device availability, which may constrain broad implementation without manufacturer support.
