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Tumor Treating Fields (TTFields) therapy is an anti-cancer treatment modality that is delivered noninvasively to the tumor site via skin-placed arrays. The therapy is US Food and Drug Administration (FDA) approved and Conformité Européenne (CE) marked for adults with newly diagnosed and recurrent glioblastoma (GBM) (grade 4 glioma in the European Union). To date, there are limited data on the safety and efficacy of TTFields therapy in patients with implanted cardiac pacemakers. Herein, we report a case of a 79-year-old male patient with GBM receiving TTFields therapy with a prior medical history of cardiac events necessitating a cardiac pacemaker. The patient presented to the emergency department in May 2021 with newly onset left-sided weakness along with seizures. Based on an initial evaluation and results of the initial computed tomography (CT) scans (May 2021), the patient was clinically diagnosed with a high-grade glioma which was later confirmed as IDH wildtype following a biopsy. He was treated with radiotherapy (40 Gy in 15 fractions), followed by adjuvant temozolomide (TMZ) (75 mg/m 2 ). TTFields therapy was initiated alongside maintenance TMZ (150 mg/m 2 ). Average TTFields therapy usage was 67% throughout the duration of treatment. Follow-up CT scans (February and May of 2022) indicated stable disease. CT scans in August 2022 showed an increase in size of a mass with heterogeneous contrast enhancement and the patient subsequently passed away in October 2022. The patient's last cardiac tests demonstrated that the pacemaker was operational with adequate cardiac function. This report suggests that TTFields therapy concomitant with an implanted electronic device may be safe in patients with GBM., Competing Interests: Authors KM and LL were employed by the company Novocure. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Novocure. The funder had the following involvement in the study: funding of medical writing support., (Copyright © 2024 Biedermann, Merrifield and Lustgarten.)

Background: Ovarian cancer is the leading cause of mortality among gynecological malignancies. Carboplatin and poly (ADP-ribose) polymerase inhibitors (PARPi) are often implemented in the treatment of ovarian cancer. Homologous recombination deficient (HRD) tumors demonstrate increased sensitivity to these treatments; however, many ovarian cancer patients are homologous recombination proficient (HRP). TTFields are non-invasive electric fields that induce an HRD-like phenotype in various cancer types. The current study aimed to investigate the impact of TTFields applied together with carboplatin or PARPi (olaparib or niraparib) in preclinical ovarian cancer models., Methods: A2780 (HRP), OVCAR3 (HRD), and A2780cis (platinum-resistant) human ovarian cancer cells were treated in vitro with TTFields (1 V/cm RMS, 200 kHz, 72 h), alone or with various drug concentrations. Treated cells were measured for cell count, colony formation, apoptosis, DNA damage, expression of DNA repair proteins, and cell cycle. In vivo , ID8-fLuc (HRP) ovarian cancer cells were inoculated intraperitoneally to C57BL/6 mice, which were then treated with either sham, TTFields (200 kHz), olaparib (50 mg/kg), or TTFields plus olaparib; over a period of four weeks. Tumor growth was analyzed using bioluminescent imaging at treatment cessation; and survival analysis was performed., Results: The nature of TTFields-drug interaction was dependent on the drug's underlying mechanism of action and on the genetic background of the cells, with synergistic interactions between TTFields and carboplatin or PARPi seen in HRP and resistant cells. Treated cells demonstrated elevated levels of DNA damage, accompanied by G2/M arrest, and induction of an HRD-like phenotype. In the tumor-bearing mice, TTFields and olaparib co-treatment resulted in reduced tumor volume and a survival benefit relative to olaparib monotherapy and to control., Conclusion: By inducing an HRD-like phenotype, TTFields sensitize HRP and resistant ovarian cancer cells to treatment with carboplatin or PARPi, potentially mitigating a-priori and de novo drug resistance, a major limitation in ovarian cancer treatment., Competing Interests: IV declares consultancy honoraria from Agenus, Akesobio, AstraZeneca, Bristol Myers Squibb, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, Elsevier, F. Hoffmann-La Roche, Genmab, GSK, Immunogen, Jazzpharma, Karyopharm, Mersana, Molecular Partners, MSD, Novocure, Novartis, Oncoinvent, OncXerna, Sanofi, Regeneron, Seagen, Sotio, Verastem Oncology, Zentalis. AC is a contracted researcher for Oncoinvent AS and Novocure and a consultant for Sotio a.s., Epics Therapeutics SA and Molecular Partners. RW is employed by Oncoinvent AS. HE, KB, AM, RM, RF, HG, ED, AH, MG, and UW are employees of Novocure and hold company stocks. MG and UW hold Novocure IP. YP is the founder of Novocure, holding company stock and IP. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Novocure Ltd. The funder had the following involvement in the study: the authors affiliated with Novocure Ltd conducted part of the study., (Copyright © 2024 Berckmans, Ene, Ben-Meir, Martinez-Conde, Wouters, Van den Ende, Van Mechelen, Monin, Frechtel-Gerzi, Gabay, Dor-On, Haber, Weinberg, Vergote, Giladi, Coosemans and Palti.)

Purpose: Multidisciplinary tumor boards (MTBs) integrate clinical, molecular, and radiological information and facilitate coordination of neuro-oncology care. During the COVID-19 pandemic, our MTB transitioned to a virtual and multi-institutional format. We hypothesized that this expansion would allow expert review of challenging neuro-oncology cases and contribute to the care of patients with limited access to specialized centers., Methods: We retrospectively reviewed records from virtual MTBs held between 04/2020-03/2021. Data collected included measures of potential clinical impact, including referrals to observational or therapeutic studies, referrals for specialized neuropathology analysis, and whether molecular findings led to a change in diagnosis and/or guided management suggestions., Results: During 25 meetings, 32 presenters discussed 44 cases. Approximately half (n = 20; 48%) involved a rare central nervous system (CNS) tumor. In 21% (n = 9) the diagnosis was changed or refined based on molecular profiling obtained at the NIH and in 36% (n = 15) molecular findings guided management. Clinical trial suggestions were offered to 31% (n = 13), enrollment in the observational NCI Natural History Study to 21% (n = 9), neuropathology review and molecular testing at the NIH to 17% (n = 7), and all received management suggestions., Conclusion: Virtual multi-institutional MTBs enable remote expert review of CNS tumors. We propose them as a strategy to facilitate expert opinions from specialized centers, especially for rare CNS tumors, helping mitigate geographic barriers to patient care and serving as a pre-screening tool for studies. Advanced molecular testing is key to obtaining a precise diagnosis, discovering potentially actionable targets, and guiding management., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)