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Modeling of intracranial tumor treating fields for the treatment of complex high-grade gliomas.

ABSTRACT: Increasing the intensity of tumor treating fields (TTF) within a tumor bed improves clinical efficacy, but reaching sufficiently high field intensities to achieve growth arrest remains challenging due in part to the insulating nature of the cranium. Using MRI-derived finite element models (FEMs) and simulations, we optimized an exhaustive set of intracranial electrode locations to obtain maximum TTF intensities in three clinically challenging high-grade glioma (HGG) cases (i.e., thalamic, left temporal, brainstem). Electric field strengths were converted into therapeutic enhancement ratios (TER) to evaluate the predicted impact of stimulation on tumor growth. Concurrently, conventional transcranial configurations were simulated/optimized for comparison. Optimized intracranial TTF were able to achieve field strengths that have previously been shown capable of inducing complete growth arrest, in 98-100% of the tumor volumes using only 0.54-0.64 A current. The reconceptualization of TTF as a targeted, intracranial therapy has the potential to provide a meaningful survival benefit to patients with HGG and other brain tumors, including those in surgically challenging, deep, or anatomically eloquent locations which may preclude surgical resection. Accordingly, such an approach may ultimately represent a paradigm shift in the use of TTFs for the treatment of brain cancer.

SUBMITTER: Segar DJ

PROVIDER: S-EPMC9886948 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Modeling of intracranial tumor treating fields for the treatment of complex high-grade gliomas.

Segar David J DJ Bernstock Joshua D JD Arnaout Omar O Bi Wenya Linda WL Friedman Gregory K GK Langer Robert R Traverso Giovanni G Rampersad Sumientra M SM

Scientific reports 20230130 1

Increasing the intensity of tumor treating fields (TTF) within a tumor bed improves clinical efficacy, but reaching sufficiently high field intensities to achieve growth arrest remains challenging due in part to the insulating nature of the cranium. Using MRI-derived finite element models (FEMs) and simulations, we optimized an exhaustive set of intracranial electrode locations to obtain maximum TTF intensities in three clinically challenging high-grade glioma (HGG) cases (i.e., thalamic, left t ...[more]

PMID: 36717682

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Project description:PurposeSince the inception of tumor treating fields (TTFields) therapy as a Food and Drug Administration-approved treatment with known clinical efficacy against recurrent and newly diagnosed glioblastoma, various in silico modeling studies have been performed in an effort to better understand the distribution of applied electric fields throughout the human body for various malignancies or metastases.Methods and materialsPostacquisition attenuation-corrected positron emission tomography-computed tomography image data sets from 2 patients with ovarian carcinoma were used to fully segment various intrapelvic and intra-abdominal gross anatomic structures. A 3-dimensional finite element mesh model was generated and then solved for the distribution of applied electric fields, rate of energy deposition, and current density at the clinical target volumes (CTVs) and other intrapelvic and intra-abdominal structures. Electric field-volume histograms, specific absorption rate-volume histograms, and current density-volume histograms were generated, by which plan quality metrics were derived from and used to evaluate relative differences in field coverage between models under various conditions.ResultsTTFields therapy distribution throughout the pelvis and abdomen was largely heterogeneous, where specifically the field intensity at the CTV was heavily influenced by surrounding anatomic structures as well as its shape and location. The electric conductivity of the CTV had a direct effect on the field strength within itself, as did the position of the arrays on the surface of the pelvis and/or abdomen.ConclusionThe combined use of electric field-volume histograms, specific absorption rate-volume histograms, current density-volume histograms, and plan quality metrics enables a personalized method to dosimetrically evaluate patients receiving TTFields therapy for ovarian carcinoma when certain patient- and tumor-specific factors are integrated with the treatment plan.

Project description:BackgroundSurgical intervention, complemented by radiotherapy and chemotherapy with temozolomide, constitutes the conventional treatment protocol for patients with newly diagnosed grade 4 glioma. We have conducted a research to evaluate the efficacy and safety of an integrated treatment regimen that incorporates tumor-treating fields with concurrent chemoradiotherapy.MethodsThis retrospective research analyzed the clinical data of 39 adults who were newly diagnosed with World Health Organization (WHO) grade 4 gliomas at the First Affiliated Hospital of Nanjing Medical University, between February 2022 and April 2023. Each participant received a concurrent treatment regimen consisting of temozolomide (75 mg/m2 daily), tumor-treating fields (200 kHz), and brain irradiation (60 Gy delivered in 30 fractions). Maintenance treatment comprised ongoing temozolomide and tumor-treating fields. Adverse events were documented in accordance with the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE 5.0) and specific grading criteria for dermatological adverse events associated with tumor-treating fields.ResultsAmong the 39 enrolled patients, disease progression was observed in 22 individuals (56.4%), with a median progression-free survival (PFS) of 14.2 months (95% confidence interval [CI]: 13.1-14.3 months). The median overall survival (OS) was 18.2 months (95% CI: 17.3 months to not reached). Patients diagnosed with glioblastoma had a median PFS of 13.1 months (95% CI: 12.9-14.2 months) and a median OS of 18.2 months (95% CI: 17.3 months to not reached). In contrast, patients diagnosed with astrocytoma had a median PFS of 14.3 months (95% CI: 12.8 months to not reached) and a median OS of 17.0 months (95% CI: 10.6 months to not reached). Twenty-five patients (64.1%) experienced dermatological adverse events, and 30 (77.0%) experienced mild hematological adverse reactions related to chemoradiotherapy.ConclusionThe application of tumor-treating fields concurrent with post-surgery chemoradiotherapy is both safe and effective for treating patients with newly diagnosed WHO grade 4 gliomas, exhibiting only limited toxicity.

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Modeling of intracranial tumor treating fields for the treatment of complex high-grade gliomas.

Publications

Modeling of intracranial tumor treating fields for the treatment of complex high-grade gliomas.

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