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

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.

Case report: tumor-treating fields prolongs IDH-mutant anaplastic astrocytoma progression-free survival and pathological evolution to glioblastoma

“…Additionally, there has been reported that the combination of TTFields with proton radiotherapy in treatment of primary GBM, and observed complete radiological response after subtotal resection (STR), chemoradiation, and TTFields. The results also suggested that adjuvant TTFields therapy can structurally affect the residual tumors after subtotal resection (19). The most common TTFields-related adverse event was array-associated skin irritation (13)(14)(15)(16).…”

Case report: Radiographic complete response of radiation-induced glioblastoma to front-line radiotherapy: A report and molecular characterization of two unique cases

“…Despite the emergence of the next-generation sequencing use in glioma in recent years to better understand disease biology and evaluate patient candidacy for nontraditional therapeutic options, this testing remains an inconsistent practice, and the relative rarity of RIGs has further limited widespread reporting of characteristic alterations. Here, we add to the limited molecular literature on RIGs with two unique clinical cases demonstrating remarkably unusual complete responses to treatment following subtotal resections on the basis of Response Assessment in Neuro-Oncology (RANO) criteria, a phenomenon not previously reported in RIGs and only rarely observed in GB independent of bevacizumab-mediated pseudoresponse (14)(15)(16)(17)(18).…”

Case Report of Complete Radiological Response of a Thalamic Glioblastoma After Treatment With Proton Therapy Followed by Temozolomide and Tumor-Treating Fields

“…Currently, there have been no reports on the combination therapy of TTFields with proton radiotherapy in primary GBM. Complete radiological response after subtotal resection, chemoradiation, and TTFields is reported (4). In this report, we present a case of a patient with biopsied thalamic GBM IDH wild-type showing a complete radiological response after chemoradiation with TMZ, proton boost therapy, and TMZ maintenance in combination with TTFields.…”