Tumor Treating Fields (TTFields) Therapy and Lomustine Chemotherapy for the Treatment of Unresectable Progressive Glioblastoma

Overview

Journal Case Rep Oncol

Publisher Karger

Specialty Oncology

Date 2024 Oct 30

PMID 39474554

Authors

Ertan Mergen

Sonja Landrock

Barbara Chizzali

Affiliations

Soon will be listed here.

Abstract

Introduction: Tumor Treating Fields (TTFields) therapy used concomitantly with maintenance temozolomide through second progression after radio-chemotherapy is associated with improved survival outcomes compared to adjuvant temozolomide alone in individuals with newly diagnosed glioblastoma (GBM). Lomustine (CCNU) is frequently used as monotherapy or concomitant with other chemotherapy regimens as second-line treatment for recurrent GBM.

Case Presentation: We report a 59-year-old female patient diagnosed with -promoter methylated, isocitrate dehydrogenase-wildtype GBM (World Health Organization Grade 4) who received TTFields therapy concomitant with first- and second-line chemotherapy following partial resection. The patient experienced tumor pseudoprogression/progression after three cycles of maintenance temozolomide/TTFields therapy and again after a further two cycles of procarbazine/CCNU/TTFields therapy, and was then switched to CCNU/TTFields therapy. During 18 months of treatment with concomitant TTFields therapy and CCNU, the patient experienced regression/reduction of both tumor volume and perifocal edema with tolerable hematotoxicity and was able to maintain a high rate of TTFields therapy usage. The patient ultimately died after developing chemotherapy-related acute myeloid leukemia.

Conclusion: This patient case is reflective of the EF-14 study outcome using TTFields therapy beyond first progression concomitantly with chemotherapy. The observations from this case suggest that TTFields therapy concomitant with CCNU is a valuable treatment modality in patients with GBM, in this context.

References

Toms S, Kim C, Nicholas G, Ram Z . Increased compliance with tumor treating fields therapy is prognostic for improved survival in the treatment of glioblastoma: a subgroup analysis of the EF-14 phase III trial. J Neurooncol. 2018; 141(2):467-473. PMC: 6342854. DOI: 10.1007/s11060-018-03057-z. View

Gagnier J, Kienle G, Altman D, Moher D, Sox H, Riley D . The CARE Guidelines: Consensus-based Clinical Case Reporting Guideline Development. Glob Adv Health Med. 2014; 2(5):38-43. PMC: 3833570. DOI: 10.7453/gahmj.2013.008. View

Gahrmann R, Smits M, Vernhout R, Taal W, Kapsas G, de Groot J . The impact of different volumetric thresholds to determine progressive disease in patients with recurrent glioblastoma treated with bevacizumab. Neurooncol Adv. 2022; 4(1):vdac032. PMC: 9000300. DOI: 10.1093/noajnl/vdac032. View

Rong L, Li N, Zhang Z . Emerging therapies for glioblastoma: current state and future directions. J Exp Clin Cancer Res. 2022; 41(1):142. PMC: 9013078. DOI: 10.1186/s13046-022-02349-7. View

Stupp R, Wong E, Kanner A, Steinberg D, Engelhard H, Heidecke V . NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer. 2012; 48(14):2192-202. DOI: 10.1016/j.ejca.2012.04.011. View

Young J, Al-Adli N, Scotford K, Cha S, Berger M . Pseudoprogression versus true progression in glioblastoma: what neurosurgeons need to know. J Neurosurg. 2023; 139(3):748-759. PMC: 10412732. DOI: 10.3171/2022.12.JNS222173. View

Karanam N, Story M . An overview of potential novel mechanisms of action underlying Tumor Treating Fields-induced cancer cell death and their clinical implications. Int J Radiat Biol. 2020; 97(8):1044-1054. DOI: 10.1080/09553002.2020.1837984. View

Lazaridis L, Schafer N, Teuber-Hanselmann S, Blau T, Schmidt T, Oster C . Tumour Treating Fields (TTFields) in combination with lomustine and temozolomide in patients with newly diagnosed glioblastoma. J Cancer Res Clin Oncol. 2019; 146(3):787-792. DOI: 10.1007/s00432-019-03106-8. View

Weller M, Le Rhun E . How did lomustine become standard of care in recurrent glioblastoma?. Cancer Treat Rev. 2020; 87:102029. DOI: 10.1016/j.ctrv.2020.102029. View

10.

Herrlinger U, Tzaridis T, Mack F, Steinbach J, Schlegel U, Sabel M . Lomustine-temozolomide combination therapy versus standard temozolomide therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter (CeTeG/NOA-09): a randomised, open-label, phase 3 trial. Lancet. 2019; 393(10172):678-688. DOI: 10.1016/S0140-6736(18)31791-4. View

11.

Davis M . Glioblastoma: Overview of Disease and Treatment. Clin J Oncol Nurs. 2016; 20(5 Suppl):S2-8. PMC: 5123811. DOI: 10.1188/16.CJON.S1.2-8. View

12.

Stupp R, Taillibert S, Kanner A, Read W, Steinberg D, Lhermitte B . Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial. JAMA. 2017; 318(23):2306-2316. PMC: 5820703. DOI: 10.1001/jama.2017.18718. View

13.

Kesari S, Ram Z . Tumor-treating fields plus chemotherapy versus chemotherapy alone for glioblastoma at first recurrence: a post hoc analysis of the EF-14 trial. CNS Oncol. 2017; 6(3):185-193. PMC: 6009218. DOI: 10.2217/cns-2016-0049. View

14.

Mummareddy N, Salwi S, Kumar N, Zhao Z, Ye F, Le C . Prognostic relevance of CSF and peri-tumoral edema volumes in glioblastoma. J Clin Neurosci. 2021; 84:1-7. DOI: 10.1016/j.jocn.2020.12.014. View

15.

Lazaridis L, Bumes E, Spille D, Schulz T, Heider S, Agkatsev S . First multicentric real-life experience with the combination of CCNU and temozolomide in newly diagnosed promoter methylated wildtype glioblastoma. Neurooncol Adv. 2022; 4(1):vdac137. PMC: 9583686. DOI: 10.1093/noajnl/vdac137. View