Abstract 4376: Tumor treating fields (TTFields) decrease proliferation of patient-derived lung cancer brain metastasis cells in vitro

Abstract

Abstract Up to 40% of all non-small cell lung cancer (NSCLC) patients will develop brain metastases during the course of their disease, with ~20-25% of patients presenting with brain metastases at the time of their initial lung cancer diagnosis. For the latter patient population, median survival is a dismal 8 months. Systemic therapies are typically ineffective at treating the brain metastases, even in cases when the extracranial disease responds to the therapy. Clinical trials utilizing TTFields therapy in patients with lung cancer brain metastases are underway. For these trials, TTFields are delivered at 150 kHz, as that is the frequency that has been determined for the treatment of primary lung cancer. In contrast, for the FDA-approved treatment of the most common malignant primary brain tumor, glioblastoma, TTFields are delivered at 200 kHz. Therefore, in this study, a patient-derived lung cancer brain metastatic cell line was assessed to compare the response to in vitro TTFields application at either 150 or 200 kHz compared to untreated control cells. Methods: Use of patient tumor tissue for this study was approved by the Wayne State University Institutional Review Board and written informed consent was obtained from the patient. An adenocarcinoma lung cancer brain metastasis (from a patient that presented with the brain metastasis at the time of diagnosis) was collected immediately following microsurgical resection. A single-cell suspension from the tumor tissue was prepared by enzymatic and mechanical disruption. After 7 passages in vitro, cells were plated on plastic coverslips (10,000 each) in DMEM/F12 media supplemented with 10% fetal bovine serum. TTFields were applied at ~1.6 V/cm at 150 or 200 kHz (groups n=4-5) with one control group. Culture media was replaced every day. After 10 days of in vitro TTFields application, cell proliferation was assessed with the XTT assay. Control vs. TTFields-treated groups were compared with two-tailed t-tests. Results: The 10-day TTFields treatment resulted in significantly reduced cellular proliferation in the cells that received 150 kHz TTFields (0.220±0.006; mean±SEM) compared to the control cells (0.250±0.009; p=0.0237) with no statistical difference between the control and the cells that received 200 kHz TTFields (0.230±0.008; p>0.05). Conclusions: Application of TTFields in vitro at 150 kHz reduced cellular proliferation in patient-derived lung cancer brain metastasis cells, with no reduction of proliferation after application of TTFields at 200 kHz. This is the first report on the in vitro effects of TTFields in a patient-derived NSCLC brain metastasis cell line. Citation Format: Sharon K. Michelhaugh, Sam Kiousis, Neil V. Klinger, Sandeep Mittal. Tumor treating fields (TTFields) decrease proliferation of patient-derived lung cancer brain metastasis cells in vitro [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4376.