Tumor Treating Fields (TTFields)—A Novel Cancer Treatment Modality: Translating Preclinical Evidence and Engineering Into a Survival Benefit with Delayed Decline in Quality of Life

Stupp, Roger; Taphoorn, Martin J.B.; Driven, L.; Taillibert, Sophie; Honnorat, Jérôme; Chen, T.C.; Šroubek, Jan; Paek, So Hyun; Escuder, Jordi; Easaw, Jay; David, Carlos A.; Kim, C.; Desai, Rajiv; Olivi, Alessandro; Kew, Yvonne; Hottinger, Andreas F.; Hegi, Monika E.; Kirson, Eilon D.; Lavy-Shahaf, Gitit; Ram, Zvi

doi:10.1016/j.ijrobp.2017.09.013

Cited by 11 publications

(10 citation statements)

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“…GBM therapy urgently needs new treatment approaches that will improve overall survival, while preserving patients’ QoL. TTFields are a new therapy approved by the FDA for newly diagnosed and recurrent GBM and are considered a fourth treatment modality that improves overall survival with a minimal impact on patients QoL 6 – 8 . In the clinical setting, an optimal frequency of 200 kHz has been established for the treatment of GBM, which is in accordance with previously published 11 , 12 , 18 as well as our own data derived from cell culture experiments that show that GaMG cells are more sensitive to TTFields than U87-MG cells.…”

Section: Discussionmentioning

confidence: 99%

“…Tumor treating fields (TTFields) at 200 kHz are a novel approved GBM treatment modality that demonstrated an improved median OS by 4.9 months in newly diagnosed GBM patients with only minor side effects in a clinical phase III trial 6 and no deterioration in QoL 7 , 8 . These alternating electric fields have a frequency range of 100–300 kHz and a field intensity of 1–3 V/cm.…”

Section: Introductionmentioning

confidence: 99%

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Effects of tumor treating fields (TTFields) on glioblastoma cells are augmented by mitotic checkpoint inhibition

et al. 2018

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Tumor treating fields (TTFields) are approved for glioblastoma (GBM) therapy. TTFields disrupt cell division by inhibiting spindle fiber formation. Spindle assembly checkpoint (SAC) inhibition combined with antimitotic drugs synergistically decreases glioma cell growth in cell culture and mice. We hypothesized that SAC inhibition will increase TTFields efficacy. Human GBM cells (U-87 MG, GaMG) were treated with TTFields (200 kHz, 1.7 V/cm) and/or the SAC inhibitor MPS1-IN-3 (IN-3, 4 µM). Cells were counted after 24, 48, and 72 h of treatment and at 24 and 72 h after end of treatment (EOT). Flow cytometry, immunofluorescence microscopy, Annexin-V staining and TUNEL assay were used to detect alterations in cell cycle and apoptosis after 72 h of treatment. The TTFields/IN-3 combination decreased cell proliferation after 72 h compared to either treatment alone (−78.6% vs. TTFields, P = 0.0337; −52.6% vs. IN-3, P = 0.0205), and reduced the number of viable cells (62% less than seeded). There was a significant cell cycle shift from G1 to G2/M phase (P < 0.0001). The apoptotic rate increased to 44% (TTFields 14%, P = 0.0002; IN-3 4%, P < 0.0001). Cell growth recovered 24 h after EOT with TTFields and IN-3 alone, but the combination led to further decrease by 92% at 72 h EOT if IN-3 treatment was continued (P = 0.0288). The combination of TTFields and SAC inhibition led to earlier and prolonged effects that significantly augmented the efficacy of TTFields and highlights a potential new targeted multimodal treatment for GBM.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of tumor treating fields (TTFields) on glioblastoma cells are augmented by mitotic checkpoint inhibition

et al. 2018

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“…As alternating electric fields of intermediate frequency and low intensity, the TTFields have been reported to slow down the growth of tumor cells while having no obvious bioeffects on normal cells [6,13,30]. However, this frequency has never been examined during the development of non-cancerous conditions such as PCO.…”

Section: Discussionmentioning

confidence: 99%

“…Tumor Treating Fields is an innovative, non-invasive and advanced therapeutic approach to various cancer therapies. This particular frequency disrupts mitosis and selectively kills rapidly dividing cancer cells by delivering continuous (over 18 h per day) low intensity, intermediate frequency, alternating electric fields (100 kHz -300 kHz) to the tumor site [30]. Tumor Treating Fields have been found very effective in the treatment of several cancers including Glioblastoma multiforme and ovarian cancers [12,17] in a preclinical setting.…”

Section: Introductionmentioning

confidence: 99%

Effect of 150 kHz electromagnetic radiation on the development of polycystic ovaries induced by estradiol Valerate in Sprague Dawley rats

2021

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Background Polycystic ovary syndrome (PCOS) is the most common complex endocrine disorder affecting approximately 2–20% of reproductive aged females. Tumour Treating Fields (100–300 kHz) is a recent innovative, non-invasive therapeutic approach to cancer therapy. This frequency as an alternative therapy for the management of polycystic ovaries has not yet been explored. Objectives To explore the effect of full-body exposure of 150 kHz Electromagnetic Radiation (EMR), on the development of polycystic ovaries in an estradiol valerate-induced PCO rat model. Method Twenty-one female adult rats were divided into three groups (n = 7 each): control, Estradiol Valerate (EV) and EV + EMR groups. The EV + EMR group was subjected to full body exposure at 150 kHz EMR continuously for eight consecutive weeks. Estradiol valerate was administered orally to induce polycystic ovaries in EV and EV + EMR groups. Body and ovarian weights were recorded and analysed. The regularity of the estrous cycle was assessed in all three groups. The histological study of ovarian tissue was carried out by haematoxylin and eosin staining. The serum concentration levels of Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH) and testosterone were measured using the ELISA method. Results The body and ovary weights did not differ significantly between the EV and EV + EMR groups. The estrous cycle was found to be irregular in both the EV and EV + EMR groups. Ovarian histology revealed near normal morphology with little or no degenerative and morphological changes in developing follicles in the exposed group. Histometrical analysis showed an increased number of developing follicles and a significant reduction in the number and size of follicular cysts (p < 0.05) in the EV + EMR group. Hormonal analysis revealed no significant difference in the testosterone and FSH levels between the EV + EMR and EV groups. However, the LH, LH/FSH ratio decreased significantly in the EV + EMR group compares to the EV group. Conclusion The 150 kHz EMR appear to have little or no degenerative and morphological changes in the developing follicles, an increased number of typical developing follicles and a significant reduction in the number and size of the follicular cysts (p < 0.05).

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“…With Tumor treating fields (TTFields), an additional treatment modality has been introduced. Its efficacy has been proven in a randomized controlled trial (2, 3). TTFields are alternating electric fields generated by a mobile device system, and applied at low intensity (0.7 V/cm) and medium frequency (200 kHz) via transducer arrays positioned on the shaved scalp in the area of the tumor (TTFields ® Instructions For Use, 2016) (4, 5).…”

Section: Introductionmentioning

confidence: 99%

Patient Reported Outcome (PRO) Among High-Grade Glioma Patients Receiving TTFields Treatment: A Two Center Observational Study

et al. 2019

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Study design: A two center, observational study.Introduction: Patient reported outcome (PRO) plays an increasingly important role in the evaluation of novel therapies for tumor patients. It has been shown that tumor treating fields (TTFields) in combination with standard therapy prolong survival in high-grade glioma (hgG) patients. But critics claim that TTFields significantly impacts patients' everyday life due to side effects and average daily time on therapy (18 h) in a patient population with very limited life expectancy and high symptom burden. However, very limited data exist on PRO for TTFields treatment.Methods: This two center, observational study describes PRO of 30 hgG patients receiving TTFields in combination with chemotherapy. We introduced a device-specific questionnaire (DSQ) addressing device-specific restrictions and impact on daily live after 2 months of therapy. Additionally following questionnaires were used: EORTC (European Organization for Research and Treatment of Cancer), QLQ-30 (Quality of life of cancer patients), QLQ BN20 (Quality of life brain cancer module), QLQ FA13 (Cancer-related fatigue), and SSUK-8 (social support).Results: Surveys have been completed by 91% of enrolled patients. EORTC QLQ-30 revealed better physical, emotional, and cognitive function than social and role function of study cohort. TTFields users reported frequently on positive social support and a low level of detrimental interactions. Seventy one percent of patients felt affected in daily life due to TTFields at least 2–3 times per week up to several times per day while maintaining high therapy compliance. Most frequent device-specific restrictions were duration of therapy (74%), size (66%), and weight (70%) of the device and changing time and bonding of the transducer arrays (66%, mean duration: 43.6 min). Restrictions on exercise of hobbies/work (63%/61%), body care (71%), and sexuality/relationship (64%) were most relevant. Seventy percent would recommend TTFields to others and 67% would reuse TTFields treatment again based on their current experience.Conclusion: The study shows that although TTFields treatment frequently affects everyday life in all aspects, therapy compliance was high and 67% of patients would reconsider TTFields for themselves. We propose that findings of PRO be taken into account for medical consultation about TTFields and in future device development to deliver high-value patient-centered care.

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Tumor Treating Fields (TTFields)—A Novel Cancer Treatment Modality: Translating Preclinical Evidence and Engineering Into a Survival Benefit with Delayed Decline in Quality of Life

Cited by 11 publications

References 0 publications

Effects of tumor treating fields (TTFields) on glioblastoma cells are augmented by mitotic checkpoint inhibition

Effects of tumor treating fields (TTFields) on glioblastoma cells are augmented by mitotic checkpoint inhibition

Effect of 150 kHz electromagnetic radiation on the development of polycystic ovaries induced by estradiol Valerate in Sprague Dawley rats

Patient Reported Outcome (PRO) Among High-Grade Glioma Patients Receiving TTFields Treatment: A Two Center Observational Study

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