Complete radiological response following subtotal resection in three glioblastoma patients under treatment with Tumor Treating Fields

Kessler,Almuth  Friederike; Linsenmann,Thomas; Westermaier,Thomas; Wolber,Wanja; Weiland,Judith; Monoranu,Camelia‑Maria; Breun,Maria; Hagemann,Carsten; Ernestus,Ralf‑Ingo; Löhr,Mario

doi:10.3892/ol.2019.11110

Complete radiological response following subtotal resection in three glioblastoma patients under treatment with Tumor Treating Fields

Authors:
- Almuth Friederike Kessler
- Thomas Linsenmann
- Thomas Westermaier
- Wanja Wolber
- Judith Weiland
- Camelia‑Maria Monoranu
- Maria Breun
- Carsten Hagemann
- Ralf‑Ingo Ernestus
- Mario Löhr
View Affiliations

Affiliations: Department of Neurosurgery, University Hospital of Würzburg, Würzburg 97080, Germany, Department of Neuropathology, Institute of Pathology, University of Würzburg, Würzburg 97080, Germany
Published online on: November 19, 2019 https://doi.org/10.3892/ol.2019.11110
Pages: 557-561

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Glioblastoma multiforme (GBM) treatment consists of surgery, radiotherapy and chemotherapy with Temozolomide (TMZ). After subtotal resection (STR), residual tumors rarely undergo spontaneous regression. Overall survival (OS) and progression‑free survival (PFS) are reduced when compared with gross total resection. There is evidence that adding Tumor Treating Fields (TTFields) to standard management may lead to a significant increase in PFS and OS. In 2015 and 2016, STR was performed in 27 patients with GBM. Of these, four subsequently received TTFields therapy in addition to chemotherapy. The present study presents a series of three patients with GBM (44‑54 years; isocitrate dehydrogenase wild-type, methylated O6‑methylguanine‑DNA methyltransferase promoter) that were treated with radiochemotherapy and TTFields after STR. Therapy with TTFields started concomitantly to TMZ following radiotherapy and was maintained for 14, 24 and 37 months. TTFields were used as monotherapy in one case, as TMZ treatment had to be stopped due to toxicity for 1 month. In all patients, TTFields therapy was well tolerated at high compliance levels, resulting in complete response (CR) after 4, 5 and 7 months, respectively. Two patients remain tumor‑free at 16 and 40 months after STR. One patient exhibited multifocal recurrence 11 months after the beginning of TTFields treatment but remains alive, presenting a mild neurological decline 24 months after starting TTFields. All three presented patients gave written informed consent for their data to be published. In conclusion, the current report detailed three patients with GBM who underwent STR and were subsequently treated with TMZ and TTFields. TTFields treatment was tolerated well and was applied accurately and with high compliance by these patients, which may have contributed to the complete response. Four of the 27 patients treated with STR received additional TTFields treatment. Three of these 4 showed a CR, while a CR was observed only 2 of the remaining 23 patients without TTFields. The current series supports the effects in clinical practice, as demonstrated in recent clinical trials. The results also demonstrated that adjuvant TTFields therapy can structurally affect residual tumors after STR.

View Figures

View References

1	Kreth FW, Thon N, Simon M, Westphal M, Schackert G, Nikkhah G, Hentschel B, Reifenberger G, Pietsch T, Weller M, et al: Gross total but not incomplete resection of glioblastoma prolongs survival in the era of radiochemotherapy. Ann Oncol. 24:3117–3123. 2013. View Article : Google Scholar : PubMed/NCBI
2	Sanai N, Polley MY, McDermott MW, Parsa AT and Berger MS: An extent of resection threshold for newly diagnosed glioblastoma. J Neurosurg. 115:3–8. 2011. View Article : Google Scholar : PubMed/NCBI
3	Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F, Lang FF, McCutcheon IE, Hassenbusch SJ, Holland E, et al: A multivariate analysis of 416 patients with glioblastoma multiforme: Prognosis, extent of resection, and survival. J Neurosurg. 95:190–198. 2001. View Article : Google Scholar : PubMed/NCBI
4	Tsitlakidis A, Foroglou N, Venetis CA, Patsalas I, Hatzisotiriou A and Selviaridis P: Biopsy versus resection in the management of malignant gliomas: A systematic review and meta-analysis. J Neurosurg. 112:1020–1032. 2010. View Article : Google Scholar : PubMed/NCBI
5	Oppenlander ME, Wolf AB, Snyder LA, Bina R, Wilson JR, Coons SW, Ashby LS, Brachman D, Nakaji P, Porter RW, et al: An extent of resection threshold for recurrent glioblastoma and its risk for neurological morbidity. J Neurosurg. 120:846–853. 2014. View Article : Google Scholar : PubMed/NCBI
6	Kirson ED, Dbalý V, Tovarys F, Vymazal J, Soustiel JF, Itzhaki A, Mordechovich D, Steinberg-Shapira S, Gurvich Z, Schneidermann R, et al: Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors. Proc Natl Acad Sci USA. 104:10152–10157. 2007. View Article : Google Scholar : PubMed/NCBI
7	Stupp R, Taillibert S, Kanner A, Read W, Steinberg D, Lhermitte B, Toms S, Idbaih A, Ahluwalia MS, Fink K, et al: Effect of tumor-treating fields plus maintenance temozolomide vs. maintenance temozolomide alone on survival in patients with glioblastoma: A Randomized Clinical Trial. JAMA. 318:2306–2316. 2017. View Article : Google Scholar : PubMed/NCBI
8	Ram Z, Kim CY, Nicholas G and Toms S: Compliance and treatment duration predict survival in a phase EF-14 trial of tumor treating fields with temozolomide in patients with newly diagnosed glioblastoma. Neuro Oncol. 19 (Suppl 6):(6): pp. vi6–vi7. 2017, https://doi.org/10.1093/neuonc/nox168.022 View Article : Google Scholar
9	Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, Degroot J, Wick W, Gilbert MR, Lassman AB, et al: Updated response assessment criteria for high-grade gliomas: Response assessment in neuro-oncology working group. J Clin Oncol. 28:1963–1972. 2010. View Article : Google Scholar : PubMed/NCBI
10	Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, et al: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 352:987–996. 2005. View Article : Google Scholar : PubMed/NCBI
11	Taphoorn MJB, Dirven L, Kanner AA, Lavy-Shahaf G, Weinberg U, Taillibert S, Toms SA, Honnorat J, Chen TC, Sroubek J, et al: Influence of treatment with tumor-treating fields on health-related quality of life of patients with newly diagnosed glioblastoma: A secondary analysis of a randomized clinical trial. JAMA Oncol. 4:495–504. 2018. View Article : Google Scholar : PubMed/NCBI
12	Stupp R, Wong ET, Kanner AA, Steinberg D, Engelhard H, Heidecke V, Kirson ED, Taillibert S, Liebermann F, Dbalý V, et al: NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: A randomised phase III trial of a novel treatment modality. Eur J Cancer. 48:2192–2202. 2012. View Article : Google Scholar : PubMed/NCBI
13	Onken J, Staub-Bartelt F, Vajkoczy P and Misch M: Acceptance and compliance of TTFields treatment among high grade glioma patients. J Neurooncol. 139:177–184. 2018. View Article : Google Scholar : PubMed/NCBI
14	Hemminki K, Liu X, Försti A, Ji J, Sundquist J and Sundquist K: Subsequent brain tumors in patients with autoimmune disease. Neuro Oncol. 15:1142–1150. 2013. View Article : Google Scholar : PubMed/NCBI
15	Ji J, Shu X, Sundquist K, Sundquist J and Hemminki K: Cancer risk in hospitalised psoriasis patients: A follow-up study in Sweden. Br J Cancer. 100:1499–1502. 2009. View Article : Google Scholar : PubMed/NCBI
16	Wang Y, Li S, Zhang Z, Chen X, You G, Yang P, Yan W, Bao ZS, Yao K, Wang L, et al: Surgical extent impacts the value of the established prognosticators in glioblastoma patients: A prospective translational study in Asia. Head Neck Oncol. 4:802012.
17	Beiko J, Suki D, Hess KR, Fox BD, Cheung V, Cabral M, Shonka N, Gilbert MR, Sawaya R, Prabhu SS, et al: IDH1 mutant malignant astrocytomas are more amenable to surgical resection and have a survival benefit associated with maximal surgical resection. Neuro Oncol. 16:81–91. 2014. View Article : Google Scholar : PubMed/NCBI
18	Bloch O, Han SJ, Cha S, Sun MZ, Aghi MK, McDermott MW, Berger MS and Parsa AT: Impact of extent of resection for recurrent glioblastoma on overall survival clinical article. J Neurosurg. 117:1032–1038. 2012. View Article : Google Scholar : PubMed/NCBI
19	Vymazal J and Wong ET: Response patterns of recurrent glioblastomas treated with tumor-treating fields. Semin Oncol. 41 (Suppl 6):S14–S24. 2014. View Article : Google Scholar : PubMed/NCBI
20	Combs SE, Rieken S, Wick W, Abdollahi A, von Deimling A, Debus J and Hartmann C: Prognostic significance of IDH-1 and MGMT in patients with glioblastoma: One step forward, and one step back? Radiat Oncol. 6:1152011. View Article : Google Scholar : PubMed/NCBI
21	Millward CP, Brodbelt AR, Haylock B, Zakaria R, Baborie A, Crooks D, Husband D, Shenoy A, Wong H and Jenkinson MD: The impact of MGMT methylation and IDH-1 mutation on long-term outcome for glioblastoma treated with chemoradiotherapy. Acta Neurochir (Wien). 158:1943–1953. 2016. View Article : Google Scholar : PubMed/NCBI
22	Yang P, Zhang W, Wang Y, Peng X, Chen B, Qiu X, Li G, Li S, Wu C, Yao K, et al: IDH mutation and MGMT promoter methylation in glioblastoma: Results of a prospective registry. Oncotarget. 6:40896–40906. 2015. View Article : Google Scholar : PubMed/NCBI