Radiation and Cancer Physics

PD 13 - Physics 8 - Poster Discussion - Outcome Analysis and Response Imaging

1110 - Correlation of TTFields Dose Density and Survival Outcomes in Newly Diagnosed Glioblastoma: A Numerical Simulation-Based Analysis of Patient Data from the EF-14 Randomized Trial.

Tuesday, October 23
4:57 PM - 5:03 PM
Location: Room 217 C/D

Correlation of TTFields Dose Density and Survival Outcomes in Newly Diagnosed Glioblastoma: A Numerical Simulation-Based Analysis of Patient Data from the EF-14 Randomized Trial.
M. T. Ballo1, Z. Bomzon2, N. Urman2, G. Lavy-Shahaf2, and S. A. Toms3; 1West Cancer Center, University of Tennessee Health Science Center, Memphis, TN, 2Novocure, Haifa, Israel, 3Neurosurgery, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI

Purpose/Objective(s): Tumor Treating Fields (TTFields) are alternating electric fields approved for the treatment of Glioblastoma (GBM). The Phase 3 EF-14 trial showed that adding TTFields to chemoradiation improves Overall Survival (OS) and Progression Free Survival (PFS) in newly diagnosed GBM. We hypothesize that increasing TTFields dose density to the tumor leads to improved patient outcome. We performed a simulation-based study investigating the co-relation between TTFields dose and OS and PFS in patients treated with TTFields during the EF-14 trial (n=466).

Materials/Methods: A total of 317 patient cases were studied. Patients who were on treatment for less than 2 months (n=87) and patients for whom MRI quality was insufficient for model creation (n=62) were excluded. For each case, a realistic head model was derived and T1-contrast images captured at baseline. The transducer array layout on each patient was obtained from EF-14 records, and the average compliance (fraction of time patient was on active treatment), and the average electrical current delivered to the patient were derived from log files of the TTFields generators used by patients. TTFields distributions were calculated using the Sim4Life software. The ”virtual” electric current delivered to a model was set to equal the average current delivered to the corresponding patient. TTFields is delivered in two almost orthogonal directions. Therefore, we defined the Local Minimum Dose Density (LMiDD) as the lower of the power densities delivered by the two fields to each point in the model, multiplied by the average compliance of the patient. For each case, average LMiDD within a tumor bed comprising the Gross Tumor Volume and a Peritumoral Boundary Zone 3 mm wide was calculated. A value of average LMiDD that divided the patients into two groups with the most statistically significant difference in OS was found. The median OS and PFS were estimated from Kaplan-Meier curves and the hazard ratio (HR) were evaluated from Cox proportional hazards model controlling for age, sex, region, performance status and MGMT status.

Results: Demographics of the two groups were similar to each other. The median OS and PFS were significantly longer when average LMiDD in the tumor bed was ≥1.6 MmW/cm3: OS (25.1 months vs. 20.9 months, p=0.002, HR=0.69) and PFS (8.8 months vs 6.5 months, p=0.006 HR=0.66). In addition the median OS and PFS were longer with TTFields when average electric field in the tumor bed was ≥1.05 V/cm OS (25.0 months vs. 21.6 months, p=0.043, HR=0.76) and PFS (8.1 months vs 7.9 months, p=0.006 HR=0.74).

Conclusion: These results show that TTFields dose density at the tumor bed correlates with patient outcome. Planning array placement to maximize delivery to the tumor as well as maximizing patient compliance will significantly improve patient outcome.

Author Disclosure: M.T. Ballo: None. Z. Bomzon: Stock; Novocure. Stock Options; Novocure. N. Urman: Stock; Novocure. Stock Options; Novocure. G. Lavy-Shahaf: Stock; Novocure. Stock Options; Novocure. S.A. Toms: Research Grant; NIH.

Matthew Ballo, MD

Disclosure:
Employment
West Cancer Center: Professor and Chair

Compensation
Novocure: Research Grants

Ownership
radiation oncology associates

Leadership
medical education research institute: Board member

Presentation(s):

Send Email for Matthew Ballo


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1110 - Correlation of TTFields Dose Density and Survival Outcomes in Newly Diagnosed Glioblastoma: A Numerical Simulation-Based Analysis of Patient Data from the EF-14 Randomized Trial.



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