Abstract 79P
Background
Tumor Treating Fields (TTF) are a novel anti-cancer modality currently approved in glioblastoma and pleural mesothelioma. Clinical trials are on-going in other cancer types. When either used alone or in conjunction with cytotoxic chemotherapies or checkpoint inhibitors, TTF have been well tolerated as reported in large clinical trials and in clinical practice. Their effect on bone- and soft-tissue sarcoma cell lines have yet been reported. We investigate effects of TTF in bone- and soft-tissue sarcomas and potential for synergism of activities with conventional systemic sarcoma therapies.
Methods
Five bone- and soft-tissue sarcoma cell lines (GCT, HT1080, ISO-HAS-B, SJSA-1 and SW982) were used in the experiments. Cells underwent 72hr 200kHz TTF treatment. Cells were collected by trypsinization at end of experiment and counted Two intensities of TTF were tested. Potential synergism with known active systemic therapeutic agents were explored.
Results
All cell lines were sensitive to 1.62V/cm TTF, ranging from 40% to 90% of cells decrease compared with their control cell numbers. Inhibitions were less pronounced in all cell lines when treated at lower intensity (0.76V/cm). HT-1080 remained most sensitive even at lower intensity, whereas no effects were observed on GCT and ISO-HAS-B. Moreover, congruent dose-response from nanomolar to micromolar concentrations of doxorubicin in control group was observed. Preliminary testing for potential synergism between TTFields and doxorubicin (D) showed concentrations of D required to achieve similar percentage of inhibitory effect is consistently lower in TTFields-treated vs. TTFields non-treated group. Pazopanib was tested specifically in ISO-HAS-B. Potential for synergistic activity was also seen.
Conclusions
TTF are active in both bone- and soft-tissue sarcomas. Magnitude of activity differs between different sarcoma subtypes with potential for TTF use as a novel therapeutic option. Inhibitory effects despite lower doses of systemic therapies when treated in conjunction with TTF opens possible strategies for dose optimization of toxic systemic treatments include possibility for dose reduction and reduction of dose-intensity.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Novocure (support of equipment and consumables).
Disclosure
H.H.F. Loong: Financial Interests, Institutional, Invited Speaker: Boehringer Ingelheim, MSD; Financial Interests, Personal, Invited Speaker: Eli Lilly, Illumina, Bayer, Guardant Health; Financial Interests, Personal, Advisory Board: Novartis, Takeda. All other authors have declared no conflicts of interest.