Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma

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.