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Correlation of Tumor Treating Fields dosimetry to survival outcomes in newly diagnosed glioblastoma: A large-scale numerical simulation-based analysis of data from the Phase 3 EF-14 randomized trial.

Al's Comment:

 This is a very technical article but basically it boils down to showing that there is a dose-response curve.  The higher the dose the better the patient does.  The dose is determined by the arrangement of the arrays around the tumor, as well as the average compliance time - which is the % of time the machine is turned on!

The differences in survival are pretty significant.  The doctor has to determine the positioning of the arrays (and articles like this will help optimize that), but the patients can work on the second part: compliance.   I find that most patients do not understand the importance of high compliance. The doctors usually say to try for about 70% compliance, but the evidence says if you can get to 90% or better, there is a big improvement.  Unlike drugs which work for days or weeks after you take them, Optune stops working the second you turn the machine off - and starts again when you turn it on.  

Posted on: 04/27/2019

  Int J Radiat Oncol Biol Phys. 2019 Apr 23. pii: S0360-3016(19)30629-7. doi: 10.1016/j.ijrobp.2019.04.008. [Epub ahead of print]
Correlation of Tumor Treating Fields dosimetry to survival outcomes in newly diagnosed glioblastoma: A large-scale numerical simulation-based analysis of data from the Phase 3 EF-14 randomized trial.
Ballo MT1, Urman N2, Lavy-Shahaf G2, Bomzon Z2, Toms S3.
Author information:
1. West Cancer Center, Memphis Tennessee. Electronic address:
2. Novocure Ltd, Haifa, Israel.
3. Warren Alpert Medical School of Brown University and Lifespan Health System, Providence, Rhode Island.
Tumor Treating Fields (TTFields) are approved for glioblastoma (GBM) based on improved overall survival (OS) and progression-free survival (PFS) in the Phase 3 EF-14 trial of newly diagnosed GBM. To test the hypothesis that increasing TTFields dose at the tumor site improves patient outcomes, we performed a simulation-based study investigating the association between TTFields dose and survival (OS and PFS) in EF-14 TTFields-treated patients.
EF-14 patient cases (N=340) were included. Realistic head models were derived from T1-contrast images captured at baseline. The transducer array layout on each patient was obtained from EF-14 records; average compliance (fraction of time patient was on active treatment), and average electrical current delivered to the patient were derived from log files of the TTFields devices used by patients. TTFields intensity distributions and power densities were calculated using a Finite Elements Method. Local Minimum Dose Density (LMiDD) was defined as the product of TTFields intensity, tissue specific conductivities, and patient compliance. The average LMiDD within a tumor bed comprising the Gross Tumor Volume and the Peritumoral Boundary Zone 3 mm wide was calculated.
The median OS and PFS were significantly longer when the average LMiDD in the tumor bed was >0.77 mW/cm3: OS (25.2 vs. 20.4 months, p=0.003, HR=0.611) and PFS (8.5 vs 6.7 months, p=0.02, HR=0.699). The median OS and PFS were longer when the average TTFields intensity was >1.06 V/cm: OS (24.3 vs. 21.6 months, p=0.03, HR=0.705) and PFS (8.1 vs 7.9 months, p=0.03, HR=0.721).
In this study we present the first reported analysis demonstrating patient-level dose responses to TTFields. We provide a rigorous definition for TTFields dose and set a conceptual framework for future work on TTFields dosimetry and treatment planning.


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