Dataset Information

CTNI-59. FIRST SAFETY ANALYSIS OF ANAPLASTIC MENINGIOMA PATIENTS TREATED WITH TUMOR TREATING FIELDS (TTFIELDS)

ABSTRACT: Abstract

BACKGROUND

Anaplastic meningioma (AM) is a rare and aggressive intracranial tumor with very limited treatment options. TTFields is an established therapy and indicated for the treatment of newly diagnosed and recurrent glioblastoma (GBM) patients. The phase 3 study METIS tests the application in another intracranial cancer type, more specifically brain metastases of non-small cell lung cancer. First preclinical data show that TTFields can reduce proliferation of patient-derived meningioma cells and one first case report of a GBM patient with an in-field meningioma was published. First clinical trials are underway to investigate the safety and efficacy in meningioma patients (NCT02847559). Here, we describe first surveillance data on anaplastic meningioma patients treated with the TTFields device indicated for GBM treatment.

METHODS

Global post-market surveillance data of patients with anaplastic meningioma were assessed employing the MedDRA body system (System organ class (SOC) and preferred terms) with data cut-off in April 2020.

RESULTS

A total of 29 patients with AM were treated since 2015 to date. The median age is 57y (range 26-74y; based on YOB). Of those 9 (31%) were female and 20 (69%) were male. 15 (52 %) patients with AM reported at least one adverse event (AE). A total of 51 AEs were reported, of those 32 were assessed by the manufacturer as potentially related to TTFields treatment. Most commonly reported were skin reactions beneath the transducer arrays (n=15). No serious adverse events related to TTFields were reported.

CONCLUSION

Here we present the first post-market surveillance data of anaplastic meningioma patients treated with TTFields. Clinical studies are warranted to investigate the safety and efficacy for the use of TTFields in anaplastic meningioma patients.

SUBMITTER: Mawrin C

PROVIDER: S-EPMC7650993 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Abstract BACKGROUND High-grade meningioma are aggressive intracranial tumors and currently only limited treatment options exist. Therefore, there is a need for further studies in search of new therapies. Tumor Treating TTFields (TTFields) therapy serves as an effective treatment against glioblastoma (GBM). Phase 3 clinical trials investigate the use of TTFields in other intracranial tumors, i.e. brain metastases of the non-small cell lung cancer. We here provide an overview of the currently available data regarding the use of TTFields in meningioma. MATERIALS AND METHODS We performed a literature search using the term “Tumor treating fields” “NovoTTF”, “TTFields” and “Optune” in combination with “Meningioma”. A brief overview of TTFields in meningioma is provided here. RESULTS In vitro studies using patient-derived anaplastic grade III meningioma cell lines showed that TTFields treatment at a frequency of 200 kHz causes a significant reduction of cell proliferation and clonogenicity as well as altering cell morphology. In a case report of a 44-year-old woman suffering from a right anterior temporal tumor as well as a distant right parietal extra-axial convexity meningioma TTFields and Temozolomide treatment was initiated. Brain MRI scans 8, 16 and 20 weeks later showed a reduction in the meningioma tumor size of 42%, 58% & 60%, respectively. Currently, two ongoing trials test the efficacy and safety of the use of TTFields in meningioma patients: a phase II single arm trial (n=27), investigating the combination of TTFields and Bevacizumab in recurrent or progressive meningioma (NCT02847559); and a pilot trial, investigating the effects of TTFields as monotherapy on recurrent atypical and anaplastic meningioma (NCT01892397). CONCLUSIONS First data indicate that TTFields might be an option in future high-grade meningioma treatment. Clinical trials need to show safety and efficacy for the TTFields treatment in meningioma patients.

Project description:BackgroundTumor Treating Fields (TTFields) are an anti-neoplastic treatment modality delivered via application of alternating electric fields using insulated transducer arrays placed directly on the skin in the region surrounding the tumor. A Phase 3 clinical trial has demonstrated the effectiveness of continuous TTFields application in patients with glioblastoma during maintenance treatment with Temozolomide. The goal of this study was to evaluate the efficacy of combining TTFields with radiation treatment (RT) in glioma cells. We also examined the effect of TTFields transducer arrays on RT distribution in a phantom model and the impact on rat skin toxicity.MethodsThe efficacy of TTFields application after induction of DNA damage by RT or bleomycin was tested in U-118 MG and LN-18 glioma cells. The alkaline comet assay was used to measure repair of DNA lesions. Repair of DNA double strand breaks (DSBs) were assessed by analyzing γH2AX or Rad51 foci. DNA damage and repair signaled by the activation pattern of phospho-ATM (pS1981) and phospho-DNA-PKcs (pS2056) was evaluated by immunoblotting. The absorption of the RT energy by transducer arrays was measured by applying RT through arrays placed on a solid-state phantom. Skin toxicities were tested in rats irradiated daily through the arrays with 2Gy (total dose of 20Gy).ResultsTTFields synergistically enhanced the efficacy of RT in glioma cells. Application of TTFields to irradiated cells impaired repair of irradiation- or chemically-induced DNA damage, possibly by blocking homologous recombination repair. Transducer arrays presence caused a minor reduction in RT intensity at 20 mm and 60 mm below the arrays, but led to a significant increase in RT dosage at the phantom surface jeopardizing the "skin sparing effect". Nevertheless, transducer arrays placed on the rat skin during RT did not lead to additional skin reactions.ConclusionsAdministration of TTFields after RT increases glioma cells treatment efficacy possibly by inhibition of DNA damage repair. These preclinical results support the application of TTFields therapy immediately after RT as a viable regimen to enhance RT outcome. Phantom measurements and animal models imply that it may be possible to leave the transducer arrays in place during RT without increasing skin toxicities.