Cancer Research
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The Clinical Application of Tumor Treating Fields Therapy in Glioblastoma
Chapters
Summary April 16th, 2019
Glioblastoma is the most common and aggressive primary brain malignancy in adults, with most tumors recurring after initial treatment. Tumor Treating Fields (TTFields) therapy is the newest treatment modality for glioblastoma. Here, we describe the proper application of TTFields-transducer arrays on patients and discuss theory and aspects of treatment.
Transcript
Tumor Treating Fields, or TTFields therapy is an accepted treatment for glioblastoma, a type of highly malignant brain cancer. It is approved by the United States Food and Drug Administration because of its demonstrated efficacy in phase three clinical trials. Our protocol is significant because we demonstrate to you, in a step-by-step fashion, the procedures required for the proper application of this therapy on a patient with glioblastoma.
It is important to note that our patient has been using this device for over four years and she has not encountered significant adverse events from this therapy. The main advantage of our technique demonstrated in this video is that we account for the surgical scars on the scalp and the indentations on the calvarium while we are placing the transducer arrays on a patient. Our procedure for the proper placement of the transducer arrays while at the same time avoiding pitfalls that may lead to complications will likely ensure the maximum delivery and usage of Tumor Treating Fields.
Our procedures may also be applicable to similar transducer array placement for tumors within the chest cavity and abdominal cavity, both of which are currently being investigated in randomized clinical trials for lung and pancreatic cancers. Begin by acquiring magnetic resonance images, or MRIs, of the patient's brain that include the margins of the scalp for treatment planning. Using axial T1 sequence MRI scans and the tools on the digital imaging and communications and medicine image viewer, obtain baseline measurements of the front to back, right to left, and right to midline, based on axial view head size, in millimeters.
Measure the superior to tentorium, right to left, and right to midline, based on the coronal view head size in millimeters. Focusing on the primary lesion, measure the front to back without the nose, right to left, right to midline, right to close tumor margin, right to far tumor margin, front to close tumor margin, and front to far tumor margin, based on the axial view tumor size in millimeters. Measure the superior to tentorium, right to left, right to midline, right to close tumor margin, right to far tumor margin, superior to close tumor margin, and superior to far tumor margin, based on the coronal view tumor size in millimeters.
When all of the measurements have been acquired, open the treatment planning software, enter the appropriate username and password, and select New Patient Transducer Array. Then, enter all of the brain and tumor lesion measurements and click Generate Transducer Array Placement. For transducer array application, first, remove the hair of the patient down the scalp with an electric razor and wipe the scalp with 70%isopropyl alcohol.
Next, remove the transducer arrays from their packaging. If the surgical scar is located at a predetermined array location, shift the four array placements two centimeters clockwise or counterclockwise. Apply the transducer array that is nearest to the surgical first, placing the connection wires to the right or left side of the body, as preferred by the patient.
Place a small gauze pad underneath the wire connector to prevent rubbing against the scalp. Apply the next transducer array in a clockwise or counterclockwise fashion, according to the predetermined array layout scheme, followed by the third and fourth transducer arrays in the same clockwise or counterclockwise fashion, keeping the location of the connection wire consistent. To assemble the Tumor Treating Fields, or TTFields device system, connect each of the four white and black color-coded connection wires to a corresponding white or black port on the connection box, making sure each connection audibly snaps into place.
The Tumor Treating Fields device system consists of a plugin power supply, lithium ion battery pack and battery charger, transducer arrays, a connection box and cable, the electric field generator, the device and battery carrying case, and finally, the portable batteries. This system is approved by the United States Food and Drug Administration for use in patients. If using the plugin power supply, connect it to the wall outlet.
If using the portable battery, connect the battery charger to a wall outlet and switch on the power to charge the battery. When fully charged, place the portable battery into the electric field generator. Insert the connector cable into the generator, making sure the arrows on the connector face up toward the DC-in label.
Then, turn on the power button on the electric field generator to start the device, and switch on the TTFields button at the top of the generator. Every three to four days, use baby oil to remove the adhesive from the skin, and apply slow, even tension with both hands to remove each array. Wash the scalp with gentle shampoo and check for dermatitis, erosions, ulcers, or infection, applying antiseptic ointment as needed.
Here are representative personalized transducer array layout as designed by the treatment planning software for the proper placement of the arrays on a patient is shown. TTFields disrupt mitosis by causing cytoplasmic blebbing, which leads to misalignment of the metaphase plate and asymmetric distribution of chromosomes. One proposed model for TTFields action on mitotic cells is that the transducer array generated electric fields perturb septin function.
The electrical conductivity and relative permittivity of the individual tissue types and their volume results in a variation of the electric field intensity and distribution within the brains of patients undergoing TTFields treatment. Therefore, transducer array placement may have an effect on the electric field strength within the tumor region. As illustrated in these images for predicting the electric field strength within an individual patient brain at adjacent axial, coronal, and sagittal slices.
Scalp sensitivity to the arrays can be alleviated by topical application of corticosteroids and by shifting the arrays, as demonstrated. These MRI images from a 56-year-old female patient diagnosed with an IDH1 mutated glioblastoma and then treated with TTFields therapy after radiation and chemotherapy, reveal a stabilized disease phenotype for over 48 months after the initial diagnosis. Tumor Treating Fields will likely have broad applications in various types of cancer.
And future research may involve combination therapies that may improve the efficacy, while minimizing side effects.
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