Article
Influence of TTFields dose on tumour progression pattern in the EF-14 trial
Einfluss der TTFields-Dosis auf das Tumorprogressionsmuster in der EF-14 Studie
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Published: | June 26, 2020 |
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Objective: In the phase III EF-14 trial on newly diagnosed glioblastoma, adding Tumor Treating Fields (TTFields) to temozolomide chemotherapy resulted in significantly improved Progression Free Survival (PFS) and Overall Survival (OS). TTFields are applied through 2 pairs of transducer arrays and an individual array layout is generated based on previous imaging. As TTFields negatively affect cell division, it was hypothesized that the distribution of TTFields dose in the brain may correlate with patterns of failure in patients.
Methods: MRI scans of 249 EF-14 treatment arm patients were used to calculate the TTFields dose and evaluate disease progression. Virtual transducer arrays were placed on realistic computational head models for each patient and the intensity distribution of TTFields was calculated by means of a Finite Element Method. The TTFields dose (in mW/cm3) was calculated by multiplying the TTFields intensity squared, tissue conductivity and average patient compliance during the initial 6 months of TTFields treatment. Regions of interest for the analysis were any residual gross tumor and an expansion margin of up to 20 mm around the residual tumor and resection cavity. For the analysis at baseline, the TTFields dose was calculated for areas containing normal brain or areas with residual tumor. Calculated doses were then correlated to subsequent recurrence.
Results: The analysis revealed that the average TTFields dose was significantly higher in regions of enhancing tumor that regressed to normal compared to normal brain that showed progression to enhancing tumor (N=194, 0.83 mW cm3 vs 0.71 mW cm3, p<0.001). Even with different expansion margins used for calculation, the results showed that TTFields doses were lower in normal brain regions that progressed to enhancing tumor (normal to tumor) compared to normal brain that remained normal (normal to normal) at the time of progression.
Conclusion: Our analysis demonstrated that a higher TTFields dose correlated with local response, confirming the effectiveness of TTFields. Therefore, it will be crucial to further improve the patient-individual planning of the TTFields dose and optimize transducer array placement. Efforts to achieve this, similar to radiotherapy planning, are ongoing. In summary, our results underline the relevance of TTFields dose at the tumor bed as well as the clinical activity of TTFields in GBM.