Al's Comment:
The last sentence may be the key to a major breakthrough. The Novocure system worked great in the lab - they were able to cure all mice with brain tumors. The initial human gbm trial also came out great. Then the large trial for patients with recurrent gbm didn't come out as good as we hoped for - it was as good or better than any other treatments used, with less side effects, but no major improvement in survival over chemotherapy and/or Avastin. However, the FDA required them to monitor all patients who use the device after it was approved. They reported initial results on all of the hundreds of patients who used the device and the results were better than in the trial. Details will hopefully be released next week.
I think the reason the results improved is experience. The doctors learned how to better aim the electrode placement and realized the importance of high compliance rates. This article brings up what might be the missing key. Theoretically, the device is tuned to kill a range of cell sizes centered on the average size of a gbm cell. This article says that perhaps the device does kill those cells where the field intensity is strong enough, but that if the electrodes are not placed correctly, the edges of the field is not strong enough, and if a gbm cell mutates into a "giant cell" they may be too large to be killed and those cells can repopulate the tumor.
We are hosting a conference in November for researchers working with the device. Hopefully we will see these issues addressed!
Posted on: 06/08/2014
World J Surg Oncol. 2014 May 22;12(1):162. [Epub ahead of print]
The effect of field strength on glioblastoma multiforme response in patients treated with the NovoTTFTM-100A system.
Turner SG, Gergel T, Wu H, Lacroix M, Toms SA.
Abstract
The NovoTTFTM-100A system is a portable device that delivers intermediate frequency alternating electric fields (TTFields, tumor treating fields) through transducer arrays arranged on the scalp. An ongoing trial is assessing its efficacy for newly diagnosed glioblastoma multiforme (GBM) and it has been FDA-approved for recurrent GBM.The fields are believed to interfere with formation of the mitotic spindle as well as to affect polar molecules at telophase, thus preventing cell division. The position of the four arrays is unique to each patient and optimized based on the patient's imaging. We present three patients with GBM in whom the fields were adjusted at recurrence and the effects of each adjustment. We believe there may be a higher risk of treatment failure on the edges of the field where the field strength may be lower.The first patient underwent subtotal resection, radiotherapy with temozolomide (TMZ), and then began NovoTTF Therapy with metronomic TMZ. She had good control for nine months; however, new bifrontal lesions developed, and her fields were adjusted with a subsequent radiographic response. Over the next five months, her tumor burden increased and death was preceded by a right insular recurrence.A second patient underwent two resections followed by radiotherapy/TMZ and NovoTTF Therapy/TMZ. Six months later, two new distal lesions were noted, and he underwent further resection with adjustment of his fields. He remained stable over the subsequent year on NovoTTF Therapy and bevacizumab.A third patient on NovoTTF Therapy/TMZ remained stable for two years but developed a small, slow growing enhancing lesion, which was resected, and his fields were adjusted accordingly. Interestingly, the pathology showed giant cell GBM with multiple syncitial-type cells.Based on these observations, we believe that field strength may play a role in 'out of field' recurrences and that either the presence of a certain field strength may select for cells that are of a different size or that tumor cells may change size to avoid the effects of the TTFields.
PMID: 24884522 [PubMed - as supplied by publisher]
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